Next Issue
Previous Issue

Table of Contents

Cells, Volume 4, Issue 4 (December 2015) , Pages 569-747

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-9
Export citation of selected articles as:
Open AccessReview
Form, Fabric, and Function of a Flagellum-Associated Cytoskeletal Structure
Cells 2015, 4(4), 726-747; https://doi.org/10.3390/cells4040726
Received: 15 September 2015 / Revised: 27 October 2015 / Accepted: 29 October 2015 / Published: 3 November 2015
Cited by 7 | Viewed by 4345 | PDF Full-text (1763 KB) | HTML Full-text | XML Full-text
Abstract
Trypanosoma brucei is a uniflagellated protist and the causative agent of African trypanosomiasis, a neglected tropical disease. The single flagellum of T. brucei is essential to a number of cellular processes such as motility, and has been a longstanding focus of scientific enquiry. [...] Read more.
Trypanosoma brucei is a uniflagellated protist and the causative agent of African trypanosomiasis, a neglected tropical disease. The single flagellum of T. brucei is essential to a number of cellular processes such as motility, and has been a longstanding focus of scientific enquiry. A number of cytoskeletal structures are associated with the flagellum in T. brucei, and one such structure—a multiprotein complex containing the repeat motif protein TbMORN1—is the focus of this review. The TbMORN1-containing complex, which was discovered less than ten years ago, is essential for the viability of the mammalian-infective form of T. brucei. The complex has an unusual asymmetric morphology, and is coiled around the flagellum to form a hook shape. Proteomic analysis using the proximity-dependent biotin identification (BioID) technique has elucidated a number of its components. Recent work has uncovered a role for TbMORN1 in facilitating protein entry into the cell, thus providing a link between the cytoskeleton and the endomembrane system. This review summarises the extant data on the complex, highlights the outstanding questions for future enquiry, and provides speculation as to its possible role in a size-exclusion mechanism for regulating protein entry. The review additionally clarifies the nomenclature associated with this topic, and proposes the adoption of the term “hook complex” to replace the former name “bilobe” to describe the complex. Full article
(This article belongs to the Special Issue Cilia and Flagella: Biogenesis and Function)
Figures

Graphical abstract

Open AccessReview
Complex Commingling: Nucleoporins and the Spindle Assembly Checkpoint
Cells 2015, 4(4), 706-725; https://doi.org/10.3390/cells4040706
Received: 19 August 2015 / Revised: 12 October 2015 / Accepted: 28 October 2015 / Published: 3 November 2015
Cited by 5 | Viewed by 2958 | PDF Full-text (1458 KB) | HTML Full-text | XML Full-text
Abstract
The segregation of the chromosomes during mitosis is an important process, in which the replicated DNA content is properly allocated into two daughter cells. To ensure their genomic integrity, cells present an essential surveillance mechanism known as the spindle assembly checkpoint (SAC), which [...] Read more.
The segregation of the chromosomes during mitosis is an important process, in which the replicated DNA content is properly allocated into two daughter cells. To ensure their genomic integrity, cells present an essential surveillance mechanism known as the spindle assembly checkpoint (SAC), which monitors the bipolar attachment of the mitotic spindle to chromosomes to prevent errors that would result in chromosome mis-segregation and aneuploidy. Multiple components of the nuclear pore complex (NPC), a gigantic protein complex that forms a channel through the nuclear envelope to allow nucleocytoplasmic exchange of macromolecules, were shown to be critical for faithful cell division and implicated in the regulation of different steps of the mitotic process, including kinetochore and spindle assembly as well as the SAC. In this review, we will describe current knowledge about the interconnection between the NPC and the SAC in an evolutional perspective, which primarily relies on the two mitotic checkpoint regulators, Mad1 and Mad2. We will further discuss the role of NPC constituents, the nucleoporins, in kinetochore and spindle assembly and the formation of the mitotic checkpoint complex during mitosis and interphase. Full article
(This article belongs to the Special Issue Nucleocytoplasmic Transport)
Figures

Graphical abstract

Open AccessReview
Role of the Polycystins in Cell Migration, Polarity, and Tissue Morphogenesis
Cells 2015, 4(4), 687-705; https://doi.org/10.3390/cells4040687
Received: 7 August 2015 / Revised: 20 October 2015 / Accepted: 26 October 2015 / Published: 30 October 2015
Cited by 9 | Viewed by 3387 | PDF Full-text (1471 KB) | HTML Full-text | XML Full-text
Abstract
Cystic kidney diseases (CKD) is a class of disorders characterized by ciliary dysfunction and, therefore, belonging to the ciliopathies. The prototype CKD is autosomal dominant polycystic kidney disease (ADPKD), whose mutated genes encode for two membrane-bound proteins, polycystin-1 (PC-1) and polycystin-2 (PC-2), of [...] Read more.
Cystic kidney diseases (CKD) is a class of disorders characterized by ciliary dysfunction and, therefore, belonging to the ciliopathies. The prototype CKD is autosomal dominant polycystic kidney disease (ADPKD), whose mutated genes encode for two membrane-bound proteins, polycystin-1 (PC-1) and polycystin-2 (PC-2), of unknown function. Recent studies on CKD-associated genes identified new mechanisms of morphogenesis that are central for establishment and maintenance of proper renal tubular diameter. During embryonic development in the mouse and lower vertebrates a convergent-extension (CE)-like mechanism based on planar cell polarity (PCP) and cellular intercalation is involved in “sculpting” the tubules into a narrow and elongated shape. Once the appropriate diameter is established, further elongation occurs through oriented cell division (OCD). The polycystins (PCs) regulate some of these essential processes. In this review we summarize recent work on the role of PCs in regulating cell migration, the cytoskeleton, and front-rear polarity. These important properties are essential for proper morphogenesis of the renal tubules and the lymphatic vessels. We highlight here several open questions and controversies. Finally, we try to outline some of the next steps required to study these processes and their relevance in physiological and pathological conditions. Full article
(This article belongs to the Special Issue The Kidney: Development, Disease and Regeneration)
Figures

Graphical abstract

Open AccessReview
Photoreceptor Sensory Cilium: Traversing the Ciliary Gate
Cells 2015, 4(4), 674-686; https://doi.org/10.3390/cells4040674
Received: 14 September 2015 / Revised: 7 October 2015 / Accepted: 9 October 2015 / Published: 15 October 2015
Cited by 14 | Viewed by 4148 | PDF Full-text (2919 KB) | HTML Full-text | XML Full-text
Abstract
Cilia are antenna-like extensions of the plasma membrane found in nearly all cell types. In the retina of the eye, photoreceptors develop unique sensory cilia. Not much was known about the mechanisms underlying the formation and function of photoreceptor cilia, largely because of [...] Read more.
Cilia are antenna-like extensions of the plasma membrane found in nearly all cell types. In the retina of the eye, photoreceptors develop unique sensory cilia. Not much was known about the mechanisms underlying the formation and function of photoreceptor cilia, largely because of technical limitations and the specific structural and functional modifications that cannot be modeled in vitro. With recent advances in microscopy techniques and molecular and biochemical approaches, we are now beginning to understand the molecular basis of photoreceptor ciliary architecture, ciliary function and its involvement in human diseases. Here, I will discuss the studies that have revealed new knowledge of how photoreceptor cilia regulate their identity and function while coping with high metabolic and trafficking demands associated with processing light signal. Full article
(This article belongs to the Special Issue Cilia and Flagella: Biogenesis and Function)
Figures

Graphical abstract

Open AccessArticle
Active Nuclear Import of Membrane Proteins Revisited
Cells 2015, 4(4), 653-673; https://doi.org/10.3390/cells4040653
Received: 10 July 2015 / Revised: 14 September 2015 / Accepted: 30 September 2015 / Published: 13 October 2015
Cited by 6 | Viewed by 2803 | PDF Full-text (3717 KB) | HTML Full-text | XML Full-text
Abstract
It is poorly understood how membrane proteins destined for the inner nuclear membrane pass the crowded environment of the Nuclear Pore Complex (NPC). For the Saccharomyces cerevisiae proteins Src1/Heh1 and Heh2, a transport mechanism was proposed where the transmembrane domains diffuse through the [...] Read more.
It is poorly understood how membrane proteins destined for the inner nuclear membrane pass the crowded environment of the Nuclear Pore Complex (NPC). For the Saccharomyces cerevisiae proteins Src1/Heh1 and Heh2, a transport mechanism was proposed where the transmembrane domains diffuse through the membrane while the extralumenal domains encoding a nuclear localization signal (NLS) and intrinsically disordered linker (L) are accompanied by transport factors and travel through the NPC. Here, we validate the proposed mechanism and explore and discuss alternative interpretations of the data. First, to disprove an interpretation where the membrane proteins become membrane embedded only after nuclear import, we present biochemical and localization data to support that the previously used, as well as newly designed reporter proteins are membrane-embedded irrespective of the presence of the sorting signals, the specific transmembrane domain (multipass or tail anchored), independent of GET, and also under conditions that the proteins are trapped in the NPC. Second, using the recently established size limit for passive diffusion of membrane proteins in yeast, and using an improved assay, we confirm active import of polytopic membrane protein with extralumenal soluble domains larger than those that can pass by diffusion on similar timescales. This reinforces that NLS-L dependent active transport is distinct from passive diffusion. Thirdly, we revisit the proposed route through the center of the NPC and conclude that the previously used trapping assay is, unfortunately, poorly suited to address the route through the NPC, and the route thus remains unresolved. Apart from the uncertainty about the route through the NPC, the data confirm active, transport factor dependent, nuclear transport of membrane-embedded mono- and polytopic membrane proteins in baker’s yeast. Full article
(This article belongs to the Special Issue Nucleocytoplasmic Transport)
Figures

Figure 1

Open AccessReview
Epithelial-to-Mesenchymal Transition in Diabetic Nephropathy: Fact or Fiction?
Cells 2015, 4(4), 631-652; https://doi.org/10.3390/cells4040631
Received: 28 August 2015 / Revised: 29 September 2015 / Accepted: 30 September 2015 / Published: 9 October 2015
Cited by 67 | Viewed by 4004 | PDF Full-text (1384 KB) | HTML Full-text | XML Full-text
Abstract
The pathophysiology of diabetic nephropathy (DN), one of the most serious complications in diabetic patients and the leading cause of end-stage renal disease worldwide, is complex and not fully elucidated. A typical hallmark of DN is the excessive deposition of extracellular matrix (ECM) [...] Read more.
The pathophysiology of diabetic nephropathy (DN), one of the most serious complications in diabetic patients and the leading cause of end-stage renal disease worldwide, is complex and not fully elucidated. A typical hallmark of DN is the excessive deposition of extracellular matrix (ECM) proteins in the glomerulus and in the renal tubulointerstitium, eventually leading to glomerulosclerosis and interstitial fibrosis. Although it is obvious that myofibroblasts play a major role in the synthesis and secretion of ECM, the origin of myofibroblasts in DN remains the subject of controversial debates. A number of studies have focused on epithelial-to-mesenchymal transition (EMT) as one source of matrix-generating fibroblasts in the diseased kidney. EMT is characterized by the acquisition of mesenchymal properties by epithelial cells, preferentially proximal tubular cells and podocytes. In this review we comprehensively review the literature and discuss arguments both for and against a function of EMT in renal fibrosis in DN. While the precise extent of the contribution to nephrotic fibrosis is certainly arduous to quantify, the picture that emerges from this extensive body of literature suggests EMT as a major source of myofibroblasts in DN. Full article
(This article belongs to the Special Issue The Kidney: Development, Disease and Regeneration)
Figures

Figure 1

Open AccessReview
Albumin and Furosemide Combination for Management of Edema in Nephrotic Syndrome: A Review of Clinical Studies
Cells 2015, 4(4), 622-630; https://doi.org/10.3390/cells4040622
Received: 7 August 2015 / Revised: 29 September 2015 / Accepted: 30 September 2015 / Published: 7 October 2015
Cited by 11 | Viewed by 4462 | PDF Full-text (673 KB) | HTML Full-text | XML Full-text
Abstract
The treatment of edema in patients with nephrotic syndrome is generally managed by dietary sodium restriction and loop diuretics. However, edema does not improve in some patients despite adequate sodium restriction and maximal dose of diuretics. In such patients, combination of albumin and [...] Read more.
The treatment of edema in patients with nephrotic syndrome is generally managed by dietary sodium restriction and loop diuretics. However, edema does not improve in some patients despite adequate sodium restriction and maximal dose of diuretics. In such patients, combination of albumin and a loop diuretic may improve edema by diuresis and natriuresis. The response to this combination of albumin and a diuretic has not been observed in all studies. The purpose of this review is to discuss the physiology of diuresis and natriuresis of this combination therapy, and provide a brief summary of various studies that have used albumin and a loop diuretic to improve diuretic-resistant edema. Also, the review suggests various reasons for not observing similar results by various investigators. Full article
(This article belongs to the Special Issue The Kidney: Development, Disease and Regeneration)
Open AccessReview
Autophagy-Related Deubiquitinating Enzymes Involved in Health and Disease
Cells 2015, 4(4), 596-621; https://doi.org/10.3390/cells4040596
Received: 2 July 2015 / Revised: 15 September 2015 / Accepted: 30 September 2015 / Published: 5 October 2015
Cited by 24 | Viewed by 3762 | PDF Full-text (900 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is an evolutionarily-conserved process that delivers diverse cytoplasmic components to the lysosomal compartment for either recycling or degradation. This involves the removal of protein aggregates, the turnover of organelles, as well as the elimination of intracellular pathogens. In this situation, when only [...] Read more.
Autophagy is an evolutionarily-conserved process that delivers diverse cytoplasmic components to the lysosomal compartment for either recycling or degradation. This involves the removal of protein aggregates, the turnover of organelles, as well as the elimination of intracellular pathogens. In this situation, when only specific cargoes should be targeted to the lysosome, the potential targets can be selectively marked by the attachment of ubiquitin in order to be recognized by autophagy-receptors. Ubiquitination plays a central role in this process, because it regulates early signaling events during the induction of autophagy and is also used as a degradation-tag on the potential autophagic cargo protein. Here, we review how the ubiquitin-dependent steps of autophagy are balanced or counteracted by deubiquitination events. Moreover, we highlight the functional role of the corresponding deubiquitinating enzymes and discuss how they might be involved in the occurrence of cancer, neurodegenerative diseases or infection with pathogenic bacteria. Full article
(This article belongs to the Special Issue Autophagy)
Figures

Figure 1

Open AccessReview
Intracellular Mono-ADP-Ribosylation in Signaling and Disease
Cells 2015, 4(4), 569-595; https://doi.org/10.3390/cells4040569
Received: 7 July 2015 / Revised: 17 September 2015 / Accepted: 21 September 2015 / Published: 25 September 2015
Cited by 34 | Viewed by 4174 | PDF Full-text (1199 KB) | HTML Full-text | XML Full-text
Abstract
A key process in the regulation of protein activities and thus cellular signaling pathways is the modification of proteins by post-translational mechanisms. Knowledge about the enzymes (writers and erasers) that attach and remove post-translational modifications, the targets that are modified and the functional [...] Read more.
A key process in the regulation of protein activities and thus cellular signaling pathways is the modification of proteins by post-translational mechanisms. Knowledge about the enzymes (writers and erasers) that attach and remove post-translational modifications, the targets that are modified and the functional consequences elicited by specific modifications, is crucial for understanding cell biological processes. Moreover detailed knowledge about these mechanisms and pathways helps to elucidate the molecular causes of various diseases and in defining potential targets for therapeutic approaches. Intracellular adenosine diphosphate (ADP)-ribosylation refers to the nicotinamide adenine dinucleotide (NAD+)-dependent modification of proteins with ADP-ribose and is catalyzed by enzymes of the ARTD (ADP-ribosyltransferase diphtheria toxin like, also known as PARP) family as well as some members of the Sirtuin family. Poly-ADP-ribosylation is relatively well understood with inhibitors being used as anti-cancer agents. However, the majority of ARTD enzymes and the ADP-ribosylating Sirtuins are restricted to catalyzing mono-ADP-ribosylation. Although writers, readers and erasers of intracellular mono-ADP-ribosylation have been identified only recently, it is becoming more and more evident that this reversible post-translational modification is capable of modulating key intracellular processes and signaling pathways. These include signal transduction mechanisms, stress pathways associated with the endoplasmic reticulum and stress granules, and chromatin-associated processes such as transcription and DNA repair. We hypothesize that mono-ADP-ribosylation controls, through these different pathways, the development of cancer and infectious diseases. Full article
(This article belongs to the Special Issue NAD+ Metabolism and Signaling)
Figures

Figure 1

Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top