Cells

28 pages, 2079 KiB

Open AccessFeature PaperReview

Vitamin B₆ and Its Role in Cell Metabolism and Physiology

by Marcelina Parra, Seth Stahl and Hanjo Hellmann

Cells 2018, 7(7), 84; https://doi.org/10.3390/cells7070084 - 22 Jul 2018

Cited by 251 | Viewed by 30971

Vitamin B₆ is one of the most central molecules in cells of living organisms. It is a critical co-factor for a diverse range of biochemical reactions that regulate basic cellular metabolism, which impact overall physiology. In the last several years, major progress [...] Read more.

Vitamin B₆ is one of the most central molecules in cells of living organisms. It is a critical co-factor for a diverse range of biochemical reactions that regulate basic cellular metabolism, which impact overall physiology. In the last several years, major progress has been accomplished on various aspects of vitamin B₆ biology. Consequently, this review goes beyond the classical role of vitamin B₆ as a cofactor to highlight new structural and regulatory information that further defines how the vitamin is synthesized and controlled in the cell. We also discuss broader applications of the vitamin related to human health, pathogen resistance, and abiotic stress tolerance. Overall, the information assembled shall provide helpful insight on top of what is currently known about the vitamin, along with addressing currently open questions in the field to highlight possible approaches vitamin B₆ research may take in the future. Full article

(This article belongs to the Special Issue 2018 Select Papers by Cells’ Editorial Board Members)

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13 pages, 910 KiB

Open AccessFeature PaperReview

TRPC3 as a Target of Novel Therapeutic Interventions

by Oleksandra Tiapko and Klaus Groschner

Cells 2018, 7(7), 83; https://doi.org/10.3390/cells7070083 - 22 Jul 2018

Cited by 44 | Viewed by 5977

Abstract

TRPC3 is one of the classical members of the mammalian transient receptor potential (TRP) superfamily of ion channels. TRPC3 is a molecule with intriguing sensory features including the direct recognition of and activation by diacylglycerols (DAG). Although TRPC3 channels are ubiquitously expressed, they [...] Read more.

TRPC3 is one of the classical members of the mammalian transient receptor potential (TRP) superfamily of ion channels. TRPC3 is a molecule with intriguing sensory features including the direct recognition of and activation by diacylglycerols (DAG). Although TRPC3 channels are ubiquitously expressed, they appear to control functions of the cardiovascular system and the brain in a highly specific manner. Moreover, a role of TRPC3 in immunity, cancer, and tissue remodeling has been proposed, generating much interest in TRPC3 as a target for pharmacological intervention. Advances in the understanding of molecular architecture and structure-function relations of TRPC3 have been the foundations for novel therapeutic approaches, such as photopharmacology and optochemical genetics of TRPC3. This review provides an account of advances in therapeutic targeting of TRPC3 channels. Full article

(This article belongs to the Special Issue TRP Channels in Health and Disease)

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13 pages, 1477 KiB

Open AccessReview

TRPM2 in the Brain: Role in Health and Disease

by Giulia Sita, Patrizia Hrelia, Agnese Graziosi, Gloria Ravegnini and Fabiana Morroni

Cells 2018, 7(7), 82; https://doi.org/10.3390/cells7070082 - 22 Jul 2018

Cited by 35 | Viewed by 5710

Abstract

Transient receptor potential (TRP) proteins have been implicated in several cell functions as non-selective cation channels, with about 30 different mammalian TRP channels having been recognized. Among them, TRP-melastatin 2 (TRPM2) is particularly involved in the response to oxidative stress and inflammation, while [...] Read more.

Transient receptor potential (TRP) proteins have been implicated in several cell functions as non-selective cation channels, with about 30 different mammalian TRP channels having been recognized. Among them, TRP-melastatin 2 (TRPM2) is particularly involved in the response to oxidative stress and inflammation, while its activity depends on the presence of intracellular calcium (Ca²⁺). TRPM2 is involved in several physiological and pathological processes in the brain through the modulation of multiple signaling pathways. The aim of the present review is to provide a brief summary of the current insights of TRPM2 role in health and disease to focalize our attention on future potential neuroprotective strategies. Full article

(This article belongs to the Section Cell Signaling)

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11 pages, 2519 KiB

Open AccessArticle

The Purified Extract from the Medicinal Plant Bacopa monnieri, Bacopaside II, Inhibits Growth of Colon Cancer Cells In Vitro by Inducing Cell Cycle Arrest and Apoptosis

by Eric Smith, Helen M. Palethorpe, Yoko Tomita, Jinxin V. Pei, Amanda R. Townsend, Timothy J. Price, Joanne P. Young, Andrea J. Yool and Jennifer E. Hardingham

Cells 2018, 7(7), 81; https://doi.org/10.3390/cells7070081 - 21 Jul 2018

Cited by 47 | Viewed by 7386

Abstract

Aquaporin-1 (AQP1), a transmembrane pore-forming molecule, facilitates the rapid movement of water and small solutes across cell membranes. We have previously shown that bacopaside II, an extract from the medicinal herb Bacopa monnieri, blocks the AQP1 water channel and impairs migration of [...] Read more.

Aquaporin-1 (AQP1), a transmembrane pore-forming molecule, facilitates the rapid movement of water and small solutes across cell membranes. We have previously shown that bacopaside II, an extract from the medicinal herb Bacopa monnieri, blocks the AQP1 water channel and impairs migration of cells that express AQP1. The aim of this study was to further elucidate the anti-tumour potential of bacopaside II in colon cancer cells. Expression of AQP1 in HT-29, SW480, SW620 and HCT116 was determined by quantitative PCR and western immunoblot. Cells were treated with bacopaside II, and morphology, growth, autophagy, cell cycle and apoptosis assessed by time-lapse microscopy, crystal violet, acridine orange, propidium iodide (PI) and annexin V/PI staining respectively. AQP1 expression was significantly higher in HT-29 than SW480, SW620 and HCT116. Bacopaside II significantly reduced growth at ≥20 µM for HT-29 and ≥15 µM for SW480, SW620 and HCT116. Inhibition of HT-29 at 20 µM was primarily mediated by G0/G1 cell cycle arrest, and at 30 µM by G2/M arrest and apoptosis. Inhibition of SW480, SW620 and HCT116 at ≥15 µM was mediated by G2/M arrest and apoptosis. These results are the first to show that bacopaside II inhibits colon cancer cell growth by inducing cell cycle arrest and apoptosis. Full article

(This article belongs to the Special Issue Aquaporins)

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9 pages, 2231 KiB

Open AccessBrief Report

Sub-Cellular Localization of Metalloproteinases in Megakaryocytes

by Alessandro Malara, Daniela Ligi, Christian A. Di Buduo, Ferdinando Mannello and Alessandra Balduini

Cells 2018, 7(7), 80; https://doi.org/10.3390/cells7070080 - 20 Jul 2018

Cited by 12 | Viewed by 4329

Abstract

Metalloproteinases (MMPs) are zinc-dependent endopeptidases that play essential roles as the mediator of matrix degradation and remodeling during organogenesis, wound healing and angiogenesis. Although MMPs were originally identified as matrixin proteases that act in the extracellular matrix, more recent research has identified members [...] Read more.

Metalloproteinases (MMPs) are zinc-dependent endopeptidases that play essential roles as the mediator of matrix degradation and remodeling during organogenesis, wound healing and angiogenesis. Although MMPs were originally identified as matrixin proteases that act in the extracellular matrix, more recent research has identified members of the MMP family in unusual locations within the cells, exerting distinct functions in addition to their established role as extracellular proteases. During thrombopoiesis, megakaryocytes (Mks) sort MMPs to nascent platelets through pseudopodial-like structure known as proplatelets. Previous studies identified gelatinases, MMP-2 and MMP-9, as a novel regulator system of Mks and the platelet function. In this work we have exploited a sensitive immunoassay to detect and quantify multiple MMP proteins and their localization, in conditioned medium and sub-cellular fractions of primary human CD34⁺-derived Mks. We provide evidence that Mks express other MMPs in addition to gelatinases MMP-2 and MMP-9, peculiar isoforms of MMP-9 and MMPs with a novel nuclear compartmentalization. Full article

(This article belongs to the Special Issue Extracellular Matrix Remodeling)

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21 pages, 2268 KiB

Open AccessFeature PaperReview

Chlamydomonas Basal Bodies as Flagella Organizing Centers

by Jenna Lynne Wingfield and Karl-Ferdinand Lechtreck

Cells 2018, 7(7), 79; https://doi.org/10.3390/cells7070079 - 17 Jul 2018

Cited by 24 | Viewed by 12284

Abstract

During ciliogenesis, centrioles convert to membrane-docked basal bodies, which initiate the formation of cilia/flagella and template the nine doublet microtubules of the flagellar axoneme. The discovery that many human diseases and developmental disorders result from defects in flagella has fueled a strong interest [...] Read more.

During ciliogenesis, centrioles convert to membrane-docked basal bodies, which initiate the formation of cilia/flagella and template the nine doublet microtubules of the flagellar axoneme. The discovery that many human diseases and developmental disorders result from defects in flagella has fueled a strong interest in the analysis of flagellar assembly. Here, we will review the structure, function, and development of basal bodies in the unicellular green alga Chlamydomonas reinhardtii, a widely used model for the analysis of basal bodies and flagella. Intraflagellar transport (IFT), a flagella-specific protein shuttle critical for ciliogenesis, was first described in C. reinhardtii. A focus of this review will be on the role of the basal bodies in organizing the IFT machinery. Full article

(This article belongs to the Section Intracellular and Plasma Membranes)

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17 pages, 563 KiB

Open AccessReview

Lamins in Lung Cancer: Biomarkers and Key Factors for Disease Progression through miR-9 Regulation?

by Julien Guinde, Diane Frankel, Sophie Perrin, Valérie Delecourt, Nicolas Lévy, Fabrice Barlesi, Philippe Astoul, Patrice Roll and Elise Kaspi

Cells 2018, 7(7), 78; https://doi.org/10.3390/cells7070078 - 16 Jul 2018

Cited by 15 | Viewed by 5652

Abstract

Lung cancer represents the primary cause of cancer death in the world. Malignant cells identification and characterization are crucial for the diagnosis and management of patients with primary or metastatic cancers. In this context, the identification of new biomarkers is essential to improve [...] Read more.

Lung cancer represents the primary cause of cancer death in the world. Malignant cells identification and characterization are crucial for the diagnosis and management of patients with primary or metastatic cancers. In this context, the identification of new biomarkers is essential to improve the differential diagnosis between cancer subtypes, to select the most appropriate therapy, and to establish prognostic correlations. Nuclear abnormalities are hallmarks of carcinoma cells and are used as cytological diagnostic criteria of malignancy. Lamins (divided into A- and B-types) are localized in the nuclear matrix comprising nuclear lamina, where they act as scaffolding protein, involved in many nuclear functions, with regulatory effects on the cell cycle and differentiation, senescence and apoptosis. Previous studies have suggested that lamins are involved in tumor development and progression with opposite results concerning their prognostic role. This review provides an overview of lamins expression in lung cancer and the relevance of these findings for disease diagnosis and prognosis. Furthermore, we discuss the link between A-type lamins expression in lung carcinoma cells and nuclear deformability, epithelial to mesenchymal transition, and metastatic potential, and which mechanisms could regulate A-type lamins expression in lung cancer, such as the microRNA miR-9. Full article

(This article belongs to the Collection Lamins and Laminopathies)

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18 pages, 2292 KiB

Open AccessArticle

Comparative and Expression Analysis of Ubiquitin Conjugating Domain-Containing Genes in Two Pyrus Species

by Yunpeng Cao, Dandan Meng, Yu Chen, Muhammad Abdullah, Qing Jin, Yi Lin and Yongping Cai

Cells 2018, 7(7), 77; https://doi.org/10.3390/cells7070077 - 16 Jul 2018

Cited by 15 | Viewed by 4121

Abstract

Ripening affects the nutritional contents and quality of fleshy fruits, and it plays an important role during the process of fruit development. Studies have demonstrated that ubiquitin-conjugating (UBC or E2) genes can regulate fruit ripening, but the characterization of UBCs in [...] Read more.

Ripening affects the nutritional contents and quality of fleshy fruits, and it plays an important role during the process of fruit development. Studies have demonstrated that ubiquitin-conjugating (UBC or E2) genes can regulate fruit ripening, but the characterization of UBCs in pear is not well documented. The recently published genome-wide sequences of Pyrus bretschneideri and Pyrus communis have allowed a comprehensive analysis of this important gene family in pear. Using bioinformatics approaches, we identified 83 (PbrUBCs) and 84 (PcpUBCs) genes from P. bretschneideri and P. communis, respectively, which were divided into 13 subfamilies. In total, 198 PbrUBC paralogous, 215 PcpUBC paralogous, and 129 orthologous gene pairs were detected. Some paralogous gene pairs were found to be distributed on the same chromosome, suggesting that these paralogs may be caused by tandem duplications. The expression patterns of most UBC genes were divergent between Pyrus bretschneideri and Pyrus communis during pear fruit development. Remarkably, the transcriptome data showed that UBC genes might play a more important role in fruit ripening for further study. This is the first report on the systematic analysis of two Pyrus UBC gene families, and these data will help further study the role of UBC genes in fruit development and ripening, as well as contribute to the functional verification of UBC genes in pear. Full article

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14 pages, 808 KiB

Open AccessFeature PaperReview

Current Status of Fibroblast Growth Factor Receptor-Targeted Therapies in Breast Cancer

by Navid Sobhani, Anna Ianza, Alberto D’Angelo, Giandomenico Roviello, Fabiola Giudici, Marina Bortul, Fabrizio Zanconati, Cristina Bottin and Daniele Generali

Cells 2018, 7(7), 76; https://doi.org/10.3390/cells7070076 - 15 Jul 2018

Cited by 34 | Viewed by 7457

Abstract

Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, metastatic breast cancer has a poor prognosis. In an era of personalized medicine, there is [...] Read more.

Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, metastatic breast cancer has a poor prognosis. In an era of personalized medicine, there is an urgent need for better knowledge of the biology leading to the disease, which can lead to the design of increasingly accurate drugs against patients’ specific molecular aberrations. Among one of the actionable targets is the fibroblast growth factor receptor (FGFR) pathway, triggered by specific ligands. The Fibroblast Growth Factor Receptors/Fibroblast Growth Factors (FGFRs/FGFs) axis offers interesting molecular targets to be pursued in clinical development. This mini-review will focus on the current knowledge of FGFR mutations, which lead to tumor formation and summarizes the state-of-the-art therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC. Full article

(This article belongs to the Special Issue Receptor Tyrosine Kinases in Health and Disease)

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26 pages, 1082 KiB

Open AccessReview

Cell Signaling in Neuronal Stem Cells

by Elkin Navarro Quiroz, Roberto Navarro Quiroz, Mostapha Ahmad, Lorena Gomez Escorcia, Jose Luis Villarreal, Cecilia Fernandez Ponce and Gustavo Aroca Martinez

Cells 2018, 7(7), 75; https://doi.org/10.3390/cells7070075 - 14 Jul 2018

Cited by 36 | Viewed by 7063

Abstract

The defining characteristic of neural stem cells (NSCs) is their ability to multiply through symmetric divisions and proliferation, and differentiation by asymmetric divisions, thus giving rise to different types of cells of the central nervous system (CNS). A strict temporal space control of [...] Read more.

The defining characteristic of neural stem cells (NSCs) is their ability to multiply through symmetric divisions and proliferation, and differentiation by asymmetric divisions, thus giving rise to different types of cells of the central nervous system (CNS). A strict temporal space control of the NSC differentiation is necessary, because its alterations are associated with neurological dysfunctions and, in some cases, death. This work reviews the current state of the molecular mechanisms that regulate the transcription in NSCs, organized according to whether the origin of the stimulus that triggers the molecular cascade in the CNS is internal (intrinsic factors) or whether it is the result of the microenvironment that surrounds the CNS (extrinsic factors). Full article

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18 pages, 6838 KiB

Open AccessReview

TRP Channel Involvement in Salivary Glands—Some Good, Some Bad

by Xibao Liu, Hwei Ling Ong and Indu Ambudkar

Cells 2018, 7(7), 74; https://doi.org/10.3390/cells7070074 - 11 Jul 2018

Cited by 29 | Viewed by 8918

Abstract

Salivary glands secrete saliva, a mixture of proteins and fluids, which plays an extremely important role in the maintenance of oral health. Loss of salivary secretion causes a dry mouth condition, xerostomia, which has numerous deleterious consequences including opportunistic infections within the oral [...] Read more.

Salivary glands secrete saliva, a mixture of proteins and fluids, which plays an extremely important role in the maintenance of oral health. Loss of salivary secretion causes a dry mouth condition, xerostomia, which has numerous deleterious consequences including opportunistic infections within the oral cavity, difficulties in eating and swallowing food, and problems with speech. Secretion of fluid by salivary glands is stimulated by activation of specific receptors on acinar cell plasma membrane and is mediated by an increase in cytosolic [Ca²⁺] ([Ca²⁺]_i). The increase in [Ca²⁺]_i regulates a number of ion channels and transporters that are required for establishing an osmotic gradient that drives water flow via aquaporin water channels in the apical membrane. The Store-Operated Ca²⁺ Entry (SOCE) mechanism, which is regulated in response to depletion of ER-Ca²⁺, determines the sustained [Ca²⁺]_i increase required for prolonged fluid secretion. Core components of SOCE in salivary gland acinar cells are Orai1 and STIM1. In addition, TRPC1 is a major and non-redundant contributor to SOCE and fluid secretion in salivary gland acinar and ductal cells. Other TRP channels that contribute to salivary flow are TRPC3 and TRPV4, while presence of others, including TRPM8, TRPA1, TRPV1, and TRPV3, have been identified in the gland. Loss of salivary gland function leads to dry mouth conditions, or xerostomia, which is clinically seen in patients who have undergone radiation treatment for head-and-neck cancers, and those with the autoimmune exocrinopathy, Sjögren’s syndrome (pSS). TRPM2 is a unique TRP channel that acts as a sensor for intracellular ROS. We will discuss recent studies reported by us that demonstrate a key role for TRPM2 in radiation-induced salivary gland dysfunction. Further, there is increasing evidence that TRPM2 might be involved in inflammatory processes. These interesting findings point to the possible involvement of TRPM2 in Sjögren’s Syndrome, although further studies will be required to identify the exact role of TRPM2 in this disease. Full article

(This article belongs to the Special Issue TRP Channels in Health and Disease)

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16 pages, 997 KiB

Open AccessFeature PaperReview

Animal Female Meiosis: The Challenges of Eliminating Centrosomes

by Oliver J. Gruss

Cells 2018, 7(7), 73; https://doi.org/10.3390/cells7070073 - 10 Jul 2018

Cited by 16 | Viewed by 8368

Abstract

Sexual reproduction requires the generation of gametes, which are highly specialised for fertilisation. Female reproductive cells, oocytes, grow up to large sizes when they accumulate energy stocks and store proteins as well as mRNAs to enable rapid cell divisions after fertilisation. At the [...] Read more.

Sexual reproduction requires the generation of gametes, which are highly specialised for fertilisation. Female reproductive cells, oocytes, grow up to large sizes when they accumulate energy stocks and store proteins as well as mRNAs to enable rapid cell divisions after fertilisation. At the same time, metazoan oocytes eliminate their centrosomes, i.e., major microtubule-organizing centres (MTOCs), during or right after the long growth phases. Centrosome elimination poses two key questions: first, how can the centrosome be re-established after fertilisation? In general, metazoan oocytes exploit sperm components, i.e., the basal body of the sperm flagellum, as a platform to reinitiate centrosome production. Second, how do most metazoan oocytes manage to build up meiotic spindles without centrosomes? Oocytes have evolved mechanisms to assemble bipolar spindles solely around their chromosomes without the guidance of pre-formed MTOCs. Female animal meiosis involves microtubule nucleation and organisation into bipolar microtubule arrays in regulated self-assembly under the control of the Ran system and nuclear transport receptors. This review summarises our current understanding of the molecular mechanism underlying self-assembly of meiotic spindles, its spatio-temporal regulation, and the key players governing this process in animal oocytes. Full article

(This article belongs to the Section Intracellular and Plasma Membranes)

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19 pages, 9071 KiB

Open AccessArticle

TRPV1-Like Immunoreactivity in the Human Locus K, a Distinct Subregion of the Cuneate Nucleus

by Marina Del Fiacco, Maria Pina Serra, Marianna Boi, Laura Poddighe, Roberto Demontis, Antonio Carai and Marina Quartu

Cells 2018, 7(7), 72; https://doi.org/10.3390/cells7070072 - 8 Jul 2018

Cited by 2 | Viewed by 4168

Abstract

The presence of transient receptor potential vanilloid type-1 receptor (TRPV1)-like immunoreactivity (LI), in the form of nerve fibres and terminals, is shown in a set of discrete gray matter subregions placed in the territory of the human cuneate nucleus. We showed previously that [...] Read more.

The presence of transient receptor potential vanilloid type-1 receptor (TRPV1)-like immunoreactivity (LI), in the form of nerve fibres and terminals, is shown in a set of discrete gray matter subregions placed in the territory of the human cuneate nucleus. We showed previously that those subregions share neurochemical and structural features with the protopathic nuclei and, after the ancient name of our town, collectively call them Locus Karalis, and briefly Locus K. TRPV1-LI in the Locus K is codistributed, though not perfectly overlapped, with that of the neuropeptides calcitonin gene-related peptide and substance P, the topography of the elements immunoreactive to the three markers, in relation to each other, reflecting that previously described in the caudal spinal trigeminal nucleus. Myelin stainings show that myelinated fibres, abundant in the cuneate, gracile and trigeminal magnocellular nuclei, are scarce in the Locus K as in the trigeminal substantia gelatinosa. Morphometric analysis shows that cell size and density of Locus K neurons are consistent with those of the trigeminal substantia gelatinosa and significantly different from those of the magnocellular trigeminal, solitary and dorsal column nuclei. We propose that Locus K is a special component of the human dorsal column nuclei. Its functional role remains to be determined, but TRPV1 appears to play a part in it. Full article

(This article belongs to the Special Issue TRP Channels in Health and Disease)

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17 pages, 1723 KiB

Open AccessFeature PaperReview

Centrosome Remodelling in Evolution

by Daisuke Ito and Mónica Bettencourt-Dias

Cells 2018, 7(7), 71; https://doi.org/10.3390/cells7070071 - 6 Jul 2018

Cited by 36 | Viewed by 7826

Abstract

The centrosome is the major microtubule organizing centre (MTOC) in animal cells. The canonical centrosome is composed of two centrioles surrounded by a pericentriolar matrix (PCM). In contrast, yeasts and amoebozoa have lost centrioles and possess acentriolar centrosomes—called the spindle pole body (SPB) [...] Read more.

The centrosome is the major microtubule organizing centre (MTOC) in animal cells. The canonical centrosome is composed of two centrioles surrounded by a pericentriolar matrix (PCM). In contrast, yeasts and amoebozoa have lost centrioles and possess acentriolar centrosomes—called the spindle pole body (SPB) and the nucleus-associated body (NAB), respectively. Despite the difference in their structures, centriolar centrosomes and SPBs not only share components but also common biogenesis regulators. In this review, we focus on the SPB and speculate how its structures evolved from the ancestral centrosome. Phylogenetic distribution of molecular components suggests that yeasts gained specific SPB components upon loss of centrioles but maintained PCM components associated with the structure. It is possible that the PCM structure remained even after centrosome remodelling due to its indispensable function to nucleate microtubules. We propose that the yeast SPB has been formed by a step-wise process; (1) an SPB-like precursor structure appeared on the ancestral centriolar centrosome; (2) it interacted with the PCM and the nuclear envelope; and (3) it replaced the roles of centrioles. Acentriolar centrosomes should continue to be a great model to understand how centrosomes evolved and how centrosome biogenesis is regulated. Full article

(This article belongs to the Section Intracellular and Plasma Membranes)

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24 pages, 851 KiB

Open AccessReview

Ion Channels and Transporters in Inflammation: Special Focus on TRP Channels and TRPC6

by Giuseppe A. Ramirez, Lavinia A. Coletto, Clara Sciorati, Enrica P. Bozzolo, Paolo Manunta, Patrizia Rovere-Querini and Angelo A. Manfredi

Cells 2018, 7(7), 70; https://doi.org/10.3390/cells7070070 - 4 Jul 2018

Cited by 38 | Viewed by 7013

Abstract

Allergy and autoimmune diseases are characterised by a multifactorial pathogenic background. Several genes involved in the control of innate and adaptive immunity have been associated with diseases and variably combine with each other as well as with environmental factors and epigenetic processes to [...] Read more.

Allergy and autoimmune diseases are characterised by a multifactorial pathogenic background. Several genes involved in the control of innate and adaptive immunity have been associated with diseases and variably combine with each other as well as with environmental factors and epigenetic processes to shape the characteristics of individual manifestations. Systemic or local perturbations in salt/water balance and in ion exchanges between the intra- and extracellular spaces or among tissues play a role. In this field, usually referred to as elementary immunology, novel evidence has been recently acquired on the role of members of the transient potential receptor (TRP) channel family in several cellular mechanisms of potential significance for the pathophysiology of the immune response. TRP canonical channel 6 (TRPC6) is emerging as a functional element for the control of calcium currents in immune-committed cells and target tissues. In fact, TRPC6 influences leukocytes’ tasks such as transendothelial migration, chemotaxis, phagocytosis and cytokine release. TRPC6 also modulates the sensitivity of immune cells to apoptosis and influences tissue susceptibility to ischemia-reperfusion injury and excitotoxicity. Here, we provide a view of the interactions between ion exchanges and inflammation with a focus on the pathogenesis of immune-mediated diseases and potential future therapeutic implications. Full article

(This article belongs to the Special Issue TRP Channels in Health and Disease)

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17 pages, 2473 KiB

Open AccessArticle

Tracking Cell Recruitment and Behavior within the Tumor Microenvironment Using Advanced Intravital Imaging Approaches

by Madison Turk, Victor Naumenko, Douglas J. Mahoney and Craig N. Jenne

Cells 2018, 7(7), 69; https://doi.org/10.3390/cells7070069 - 3 Jul 2018

Cited by 13 | Viewed by 6320

Abstract

Recent advances in imaging technology have made it possible to track cellular recruitment and behavior within the vasculature of living animals in real-time. Using approaches such as resonant scanning confocal and multiphoton intravital microscopy (IVM), we are now able to observe cells within [...] Read more.

Recent advances in imaging technology have made it possible to track cellular recruitment and behavior within the vasculature of living animals in real-time. Using approaches such as resonant scanning confocal and multiphoton intravital microscopy (IVM), we are now able to observe cells within the intact tumor microenvironment of a mouse. We are able to follow these cells for extended periods of time (hours) and can characterize how specific cell types (T cells, neutrophils, monocytes) interact with the tumor vasculature and cancer cells. This approach provides greater insight into specific cellular behaviors and cell–cell interactions than conventional techniques such as histology and flow cytometry. In this report, we describe the surgical preparation of animals to expose the tumor and both resonant scanning confocal and multiphoton imaging approaches used to track leukocyte recruitment, adhesion, and behavior within the tumor microenvironment. We present techniques for the measurement and quantification of leukocyte behavior within the bloodstream and tumor interstitium. The use of IVM to study leukocyte behavior within the tumor microenvironment provides key information not attainable with other approaches, that will help shape the development of better, more effective anticancer drugs and therapeutic approaches. Full article

(This article belongs to the Special Issue Innovative Methods to Monitor Single Live Cells)

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20 pages, 1793 KiB

Open AccessReview

Metabolic Stress in the Immune Function of T Cells, Macrophages and Dendritic Cells

by Charlotte Domblides, Lydia Lartigue and Benjamin Faustin

Cells 2018, 7(7), 68; https://doi.org/10.3390/cells7070068 - 29 Jun 2018

Cited by 54 | Viewed by 8090

Abstract

Innate and adaptive immune cells from myeloid and lymphoid lineages resolve host infection or cell stress by mounting an appropriate and durable immune response. Upon sensing of cellular insults, immune cells become activated and undergo rapid and efficient functional changes to unleash biosynthesis [...] Read more.

Innate and adaptive immune cells from myeloid and lymphoid lineages resolve host infection or cell stress by mounting an appropriate and durable immune response. Upon sensing of cellular insults, immune cells become activated and undergo rapid and efficient functional changes to unleash biosynthesis of macromolecules, proliferation, survival, and trafficking; unprecedented events among other mammalian cells within the host. These changes must become operational within restricted timing to rapidly control the insult and to avoid tissue damage and pathogen spread. Such changes occur at high energy cost. Recent advances have established that plasticity of immune functions occurs in distinct metabolic stress features. Evidence has accumulated to indicate that specific metabolic signatures dictate appropriate immune functions in both innate and adaptive immunity. Importantly, recent studies have shed light on whether successfully manipulating particular metabolic targets is sufficient to modulate immune function and polarization, thereby offering strong therapeutic potential for various common immune-mediated diseases, including inflammation and autoimmune-associated diseases and cancer. In this review, we detail how cellular metabolism controls immune function and phenotype within T cells and macrophages particularly, and the distinct molecular metabolic programming and targets instrumental to engage this regulation. Full article

(This article belongs to the Special Issue Cellular Stress Response in Health and Disease)

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16 pages, 3097 KiB

Open AccessFeature PaperReview

Rapid Evolution of Sperm Produces Diverse Centriole Structures that Reveal the Most Rudimentary Structure Needed for Function

by Tomer Avidor-Reiss

Cells 2018, 7(7), 67; https://doi.org/10.3390/cells7070067 - 26 Jun 2018

Cited by 37 | Viewed by 9114

Abstract

Centrioles are ancient subcellular protein-based organelles that maintain a conserved number and structure across many groups of eukaryotes. Centriole number (two per cells) is tightly regulated; each pre-existing centriole nucleates only one centriole as the cell prepares for division. The structure of centrioles [...] Read more.

Centrioles are ancient subcellular protein-based organelles that maintain a conserved number and structure across many groups of eukaryotes. Centriole number (two per cells) is tightly regulated; each pre-existing centriole nucleates only one centriole as the cell prepares for division. The structure of centrioles is barrel-shaped, with a nine-fold symmetry of microtubules. This organization of microtubules is essential for the ancestral function of centriole–cilium nucleation. In animal cells, centrioles have gained an additional role: recruiting pericentriolar material (PCM) to form a centrosome. Therefore, it is striking that in animal spermatozoa, the centrioles have a remarkable diversity of structures, where some are so anomalous that they are referred to as atypical centrioles and are barely recognizable. The atypical centriole maintains the ability to form a centrosome and nucleate a new centriole, and therefore reveals the most rudimentary structure that is needed for centriole function. However, the atypical centriole appears to be incapable of forming a cilium. Here, we propose that the diversity in sperm centriole structure is due to rapid evolution in the shape of the spermatozoa head and neck. The enhanced diversity may be driven by a combination of direct selection for novel centriole functions and pleiotropy, which eliminates centriole properties that are dispensable in the spermatozoa function. Full article

(This article belongs to the Section Intracellular and Plasma Membranes)

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Graphical abstract

13 pages, 2418 KiB

Open AccessFeature PaperArticle

The Desmosomal Cadherin Desmoglein-2 Experiences Mechanical Tension as Demonstrated by a FRET-Based Tension Biosensor Expressed in Living Cells

by Sindora R. Baddam, Paul T. Arsenovic, Vani Narayanan, Nicole R. Duggan, Carl R. Mayer, Shaston T. Newman, Dahlia A. Abutaleb, Abhinav Mohan, Andrew P. Kowalczyk and Daniel E. Conway

Cells 2018, 7(7), 66; https://doi.org/10.3390/cells7070066 - 26 Jun 2018

Cited by 33 | Viewed by 7011

Abstract

Cell-cell junctions are critical structures in a number of tissues for mechanically coupling cells together, cell-to-cell signaling, and establishing a barrier. In many tissues, desmosomes are an important component of cell-cell junctions. Loss or impairment of desmosomes presents with clinical phenotypes in the [...] Read more.

Cell-cell junctions are critical structures in a number of tissues for mechanically coupling cells together, cell-to-cell signaling, and establishing a barrier. In many tissues, desmosomes are an important component of cell-cell junctions. Loss or impairment of desmosomes presents with clinical phenotypes in the heart and skin as cardiac arrhythmias and skin blistering, respectively. Because heart and skin are tissues that are subject to large mechanical stresses, we hypothesized that desmosomes, similar to adherens junctions, would also experience significant tensile loading. To directly measure mechanical forces across desmosomes, we developed and validated a desmoglein-2 (DSG-2) force sensor, using the existing TSmod Förster resonance energy transfer (FRET) force biosensor. When expressed in human cardiomyocytes, the force sensor reported high tensile loading of DSG-2 during contraction. Additionally, when expressed in Madin-Darby canine kidney (MDCK) epithelial or epidermal (A431) monolayers, the sensor also reported tensile loading. Finally, we observed higher DSG-2 forces in 3D MDCK acini when compared to 2D monolayers. Taken together, our results show that desmosomes experience low levels of mechanical tension in resting cells, with significantly higher forces during active loading. Full article

(This article belongs to the Special Issue Cell Adhesion Molecules)

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20 pages, 3038 KiB

Open AccessFeature PaperArticle

Osmotic Stress Blocks Mobility and Dynamic Regulation of Centriolar Satellites

by Julie C. Nielsen, Cathrine Nordgaard, Maxim A. X. Tollenaere and Simon Bekker-Jensen

Cells 2018, 7(7), 65; https://doi.org/10.3390/cells7070065 - 22 Jun 2018

Cited by 5 | Viewed by 5414

Abstract

Centriolar satellites (CS) are small proteinaceous granules that cluster around the centrosome and serve as cargo vehicles for centrosomal proteins. It is generally accepted that CS support a number of canonical and specialized centrosome functions. Consequently, these highly dynamic structures are the target [...] Read more.

Centriolar satellites (CS) are small proteinaceous granules that cluster around the centrosome and serve as cargo vehicles for centrosomal proteins. It is generally accepted that CS support a number of canonical and specialized centrosome functions. Consequently, these highly dynamic structures are the target of regulation by several cellular signalling pathways. Two decades of research have led to the identification of a large number of molecular components and new biological roles of CS. Here, we summarize the latest advances in the continuous efforts to uncover the compositional, functional, dynamic and regulatory aspects of CS. We also report on our discovery that osmotic stress conditions render CS immobile and insensitive to remodelling. Upon a range of p38-activating stimuli, MK2 phosphorylates the CS component CEP131, resulting in 14-3-3 binding and a block to CS formation. This normally manifests as a rapid cellular depletion of satellites. In the case of osmotic stress, a potent inducer of p38 activity, CS translocation and dissolution is blocked, with the net result that satellites persist in an immobile state directly adjacent to the centrosome. Our results highlight a unique scenario where p38 activation and CS depletion is uncoupled, with potential implications for physiological and pathological osmotic stress responses. Full article

(This article belongs to the Section Intracellular and Plasma Membranes)

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12 pages, 1838 KiB

Open AccessFeature PaperArticle

Hypoxia and IF₁ Expression Promote ROS Decrease in Cancer Cells

by Gianluca Sgarbi, Giulia Gorini, Francesca Liuzzi, Giancarlo Solaini and Alessandra Baracca

Cells 2018, 7(7), 64; https://doi.org/10.3390/cells7070064 - 21 Jun 2018

Cited by 37 | Viewed by 6462

Abstract

The role of reactive oxygen species (ROS) in the metabolic reprogramming of cells adapted to hypoxia and the interplay between ROS and hypoxia in malignancy is under debate. Here, we examined how ROS levels are modulated by hypoxia in human cancer compared to [...] Read more.

The role of reactive oxygen species (ROS) in the metabolic reprogramming of cells adapted to hypoxia and the interplay between ROS and hypoxia in malignancy is under debate. Here, we examined how ROS levels are modulated by hypoxia in human cancer compared to untransformed cells. Short time exposure (20 min) of either fibroblasts or 143B osteosarcoma cells to low oxygen tension down to 0.5% induced a significant decrease of the cellular ROS level, as detected by the CellROX fluorescent probe (−70%). Prolonging the cells’ exposure to hypoxia for 24 h, ROS decreased further, reaching nearly 20% of the normoxic value. In this regard, due to the debated role of the endogenous inhibitor protein (IF₁) of the ATP synthase complex in cancer cell bioenergetics, we investigated whether IF₁ is involved in the control of ROS generation under severe hypoxic conditions. A significant ROS content decrease was observed in hypoxia in both IF₁-expressing and IF₁- silenced cells compared to normoxia. However, IF₁-silenced cells showed higher ROS levels compared to IF1-containing cells. In addition, the MitoSOX Red-measured superoxide level of all the hypoxic cells was significantly lower compared to normoxia; however, the decrease was milder than the marked drop of ROS content. Accordingly, the difference between IF₁-expressing and IF₁-silenced cells was smaller but significant in both normoxia and hypoxia. In conclusion, the interplay between ROS and hypoxia and its modulation by IF₁ have to be taken into account to develop therapeutic strategies against cancer. Full article

(This article belongs to the Section Mitochondria)

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Cells, Volume 7, Issue 7 (July 2018) – 21 articles

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