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15 pages, 2329 KiB

Open AccessCommunication

Centrosome Positioning in Migrating Dictyostelium Cells

by Hellen Ishikawa-Ankerhold, Janina Kroll, Dominic van den Heuvel, Jörg Renkawitz and Annette Müller-Taubenberger

Cells 2022, 11(11), 1776; https://doi.org/10.3390/cells11111776 - 29 May 2022

Cited by 6 | Viewed by 7787

Abstract

Directional cell migration and the establishment of polarity play an important role in development, wound healing, and host cell defense. While actin polymerization provides the driving force at the cell front, the microtubule network assumes a regulatory function, in coordinating front protrusion and [...] Read more.

Directional cell migration and the establishment of polarity play an important role in development, wound healing, and host cell defense. While actin polymerization provides the driving force at the cell front, the microtubule network assumes a regulatory function, in coordinating front protrusion and rear retraction. By using Dictyostelium discoideum cells as a model for amoeboid movement in different 2D and 3D environments, the position of the centrosome relative to the nucleus was analyzed using live-cell microscopy. Our results showed that the centrosome was preferentially located rearward of the nucleus under all conditions tested for directed migration, while the nucleus was oriented toward the expanding front. When cells are hindered from straight movement by obstacles, the centrosome is displaced temporarily from its rearward location to the side of the nucleus, but is reoriented within seconds. This relocalization is supported by the presence of intact microtubules and their contact with the cortex. The data suggest that the centrosome is responsible for coordinating microtubules with respect to the nucleus. In summary, we have analyzed the orientation of the centrosome during different modes of migration in an amoeboid model and present evidence that the basic principles of centrosome positioning and movement are conserved between Dictyostelium and human leukocytes. Full article

(This article belongs to the Special Issue Comparative Biology of Microtubule Organization in Eukaryotes)

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21 pages, 6524 KiB

Open AccessArticle

SIN-Like Pathway Kinases Regulate the End of Mitosis in the Methylotrophic Yeast Ogataea polymorpha

by Hiromi Maekawa, Shen Jiangyan, Kaoru Takegawa and Gislene Pereira

Cells 2022, 11(9), 1519; https://doi.org/10.3390/cells11091519 - 30 Apr 2022

Cited by 1 | Viewed by 2957

Abstract

The mitotic exit network (MEN) is a conserved signalling pathway essential for the termination of mitosis in the budding yeast Saccharomyces cerevisiae. All MEN components are highly conserved in the methylotrophic budding yeast Ogataea polymorpha, except for Cdc15 kinase. Instead, we [...] Read more.

The mitotic exit network (MEN) is a conserved signalling pathway essential for the termination of mitosis in the budding yeast Saccharomyces cerevisiae. All MEN components are highly conserved in the methylotrophic budding yeast Ogataea polymorpha, except for Cdc15 kinase. Instead, we identified two essential kinases OpHcd1 and OpHcd2 (homologue candidate of ScCdc15) that are homologous to SpSid1 and SpCdc7, respectively, components of the septation initiation network (SIN) of the fission yeast Schizosaccharomyces pombe. Conditional mutants for OpHCD1 and OpHCD2 exhibited significant delay in late anaphase and defective cell separation, suggesting that both genes have roles in mitotic exit and cytokinesis. Unlike Cdc15 in S. cerevisiae, the association of OpHcd1 and OpHcd2 with the yeast centrosomes (named spindle pole bodies, SPBs) is restricted to the SPB in the mother cell body. SPB localisation of OpHcd2 is regulated by the status of OpTem1 GTPase, while OpHcd1 requires the polo-like kinase OpCdc5 as well as active Tem1 to ensure the coordination of mitotic exit (ME) signalling and cell cycle progression. Our study suggests that the divergence of molecular mechanisms to control the ME-signalling pathway as well as the loss of Sid1/Hcd1 kinase in the MEN occurred relatively recently during the evolution of budding yeast. Full article

(This article belongs to the Special Issue Comparative Biology of Microtubule Organization in Eukaryotes)

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18 pages, 4239 KiB

Open AccessArticle

Mitotic Maturation Compensates for Premature Centrosome Splitting and PCM Loss in Human cep135 Knockout Cells

by Zhenzhen Chu and Oliver J. Gruss

Cells 2022, 11(7), 1189; https://doi.org/10.3390/cells11071189 - 1 Apr 2022

Cited by 4 | Viewed by 3212

Abstract

Centrosomes represent main microtubule organizing centers (MTOCs) in animal cells. Their duplication in S-phase enables the establishment of two MTOCs in M-phase that define the poles of the spindle and ensure equal distribution of chromosomes and centrosomes to the two daughter cells. While [...] Read more.

Centrosomes represent main microtubule organizing centers (MTOCs) in animal cells. Their duplication in S-phase enables the establishment of two MTOCs in M-phase that define the poles of the spindle and ensure equal distribution of chromosomes and centrosomes to the two daughter cells. While key functions of many centrosomal proteins have been addressed in RNAi experiments and chronic knockdown, knockout experiments with complete loss of function in all cells enable quantitative analysis of cellular phenotypes at all cell-cycle stages. Here, we show that the centriolar satellite proteins SSX2IP and WDR8 and the centriolar protein CEP135 form a complex before centrosome assembly in vertebrate oocytes and further functionally interact in somatic cells with established centrosomes. We present stable knockouts of SSX2IP, WDR8, and CEP135 in human cells. While loss of SSX2IP and WDR8 are compensated for, cep135 knockout cells display compromised PCM recruitment, reduced MTOC function, and premature centrosome splitting with imbalanced PCMs. Defective cep135 knockout centrosomes, however, manage to establish balanced spindle poles, allowing unperturbed mitosis and regular cell proliferation. Our data show essential functions of CEP135 in interphase MTOCs and demonstrate that loss of individual functions of SSX2IP, WDR8, and CEP135 are fully compensated for in mitosis. Full article

(This article belongs to the Special Issue Comparative Biology of Microtubule Organization in Eukaryotes)

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22 pages, 5778 KiB

Open AccessArticle

Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers

by Rebecca A. Buchwalter, Sarah C. Ogden, Sara B. York, Li Sun, Chunfeng Zheng, Christy Hammack, Yichen Cheng, Jieyan V. Chen, Allaura S. Cone, David G. Meckes, Jr., Hengli Tang and Timothy L. Megraw

Cells 2021, 10(12), 3335; https://doi.org/10.3390/cells10123335 - 27 Nov 2021

Cited by 9 | Viewed by 4322

Abstract

Zika virus (ZIKV) became a global health concern in 2016 due to its links to congenital microcephaly and other birth defects. Flaviviruses, including ZIKV, reorganize the endoplasmic reticulum (ER) to form a viroplasm, a compartment where virus particles are assembled. Microtubules (MTs) and [...] Read more.

Zika virus (ZIKV) became a global health concern in 2016 due to its links to congenital microcephaly and other birth defects. Flaviviruses, including ZIKV, reorganize the endoplasmic reticulum (ER) to form a viroplasm, a compartment where virus particles are assembled. Microtubules (MTs) and microtubule-organizing centers (MTOCs) coordinate structural and trafficking functions in the cell, and MTs also support replication of flaviviruses. Here we investigated the roles of MTs and the cell’s MTOCs on ZIKV viroplasm organization and virus production. We show that a toroidal-shaped viroplasm forms upon ZIKV infection, and MTs are organized at the viroplasm core and surrounding the viroplasm. We show that MTs are necessary for viroplasm organization and impact infectious virus production. In addition, the centrosome and the Golgi MTOC are closely associated with the viroplasm, and the centrosome coordinates the organization of the ZIKV viroplasm toroidal structure. Surprisingly, viroplasm formation and virus production are not significantly impaired when infected cells have no centrosomes and impaired Golgi MTOC, and we show that MTs are anchored to the viroplasm surface in these cells. We propose that the viroplasm is a site of MT organization, and the MTs organized at the viroplasm are sufficient for efficient virus production. Full article

(This article belongs to the Special Issue Comparative Biology of Microtubule Organization in Eukaryotes)

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19 pages, 10890 KiB

Open AccessArticle

Cep192, a Novel Missing Link between the Centrosomal Core and Corona in Dictyostelium Amoebae

by Valentin Pitzen, Sophia Sander, Otto Baumann, Ralph Gräf and Irene Meyer

Cells 2021, 10(9), 2384; https://doi.org/10.3390/cells10092384 - 10 Sep 2021

Cited by 8 | Viewed by 3314

Abstract

The Dictyostelium centrosome is a nucleus-associated body with a diameter of approx. 500 nm. It contains no centrioles but consists of a cylindrical layered core structure surrounded by a microtubule-nucleating corona. At the onset of mitosis, the corona disassembles and the core structure [...] Read more.

The Dictyostelium centrosome is a nucleus-associated body with a diameter of approx. 500 nm. It contains no centrioles but consists of a cylindrical layered core structure surrounded by a microtubule-nucleating corona. At the onset of mitosis, the corona disassembles and the core structure duplicates through growth, splitting, and reorganization of the outer core layers. During the last decades our research group has characterized the majority of the 42 known centrosomal proteins. In this work we focus on the conserved, previously uncharacterized Cep192 protein. We use superresolution expansion microscopy (ExM) to show that Cep192 is a component of the outer core layers. Furthermore, ExM with centrosomal marker proteins nicely mirrored all ultrastructurally known centrosomal substructures. Furthermore, we improved the proximity-dependent biotin identification assay (BioID) by adapting the biotinylase BioID2 for expression in Dictyostelium and applying a knock-in strategy for the expression of BioID2-tagged centrosomal fusion proteins. Thus, we were able to identify various centrosomal Cep192 interaction partners, including CDK5RAP2, which was previously allocated to the inner corona structure, and several core components. Studies employing overexpression of GFP-Cep192 as well as depletion of endogenous Cep192 revealed that Cep192 is a key protein for the recruitment of corona components during centrosome biogenesis and is required to maintain a stable corona structure. Full article

(This article belongs to the Special Issue Comparative Biology of Microtubule Organization in Eukaryotes)

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14 pages, 21528 KiB

Open AccessCommunication

Genetic Instability Due to Spindle Anomalies Visualized in Mutants of Dictyostelium

by Mary Ecke, Jana Prassler and Günther Gerisch

Cells 2021, 10(9), 2240; https://doi.org/10.3390/cells10092240 - 29 Aug 2021

Cited by 1 | Viewed by 2267

Abstract

Aberrant centrosome activities in mutants of Dictyostelium discoideum result in anomalies of mitotic spindles that affect the reliability of chromosome segregation. Genetic instabilities caused by these deficiencies are tolerated in multinucleate cells, which can be produced by electric-pulse induced cell fusion as a [...] Read more.

Aberrant centrosome activities in mutants of Dictyostelium discoideum result in anomalies of mitotic spindles that affect the reliability of chromosome segregation. Genetic instabilities caused by these deficiencies are tolerated in multinucleate cells, which can be produced by electric-pulse induced cell fusion as a source for aberrations in the mitotic apparatus of the mutant cells. Dual-color fluorescence labeling of the microtubule system and the chromosomes in live cells revealed the variability of spindle arrangements, of centrosome-nuclear interactions, and of chromosome segregation in the atypical mitoses observed. Full article

(This article belongs to the Special Issue Comparative Biology of Microtubule Organization in Eukaryotes)

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Review

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10 pages, 714 KiB

Open AccessReview

Role of Polo-like Kinases Plk1 and Plk4 in the Initiation of Centriole Duplication—Impact on Cancer

by Ingrid Hoffmann

Cells 2022, 11(5), 786; https://doi.org/10.3390/cells11050786 - 24 Feb 2022

Cited by 14 | Viewed by 4019

Abstract

Centrosomes nucleate and anchor microtubules and therefore play major roles in spindle formation and chromosome segregation during mitosis. Duplication of the centrosome occurs, similar to DNA, only once during the cell cycle. Aberration of the centrosome number is common in human tumors. At [...] Read more.

Centrosomes nucleate and anchor microtubules and therefore play major roles in spindle formation and chromosome segregation during mitosis. Duplication of the centrosome occurs, similar to DNA, only once during the cell cycle. Aberration of the centrosome number is common in human tumors. At the core of centriole duplication is the conserved polo-like kinase 4, Plk4, and two structural proteins, STIL and Sas-6. In this review, I summarize and discuss developments in our understanding of the first steps of centriole duplication and their regulation. Full article

(This article belongs to the Special Issue Comparative Biology of Microtubule Organization in Eukaryotes)

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29 pages, 3854 KiB

Open AccessReview

Estrogens—Origin of Centrosome Defects in Human Cancer?

by Miriam Bühler and Ailine Stolz

Cells 2022, 11(3), 432; https://doi.org/10.3390/cells11030432 - 27 Jan 2022

Cited by 3 | Viewed by 7415

Abstract

Estrogens are associated with a variety of diseases and play important roles in tumor development and progression. Centrosome defects are hallmarks of human cancers and contribute to ongoing chromosome missegragation and aneuploidy that manifest in genomic instability and tumor progression. Although several mechanisms [...] Read more.

Estrogens are associated with a variety of diseases and play important roles in tumor development and progression. Centrosome defects are hallmarks of human cancers and contribute to ongoing chromosome missegragation and aneuploidy that manifest in genomic instability and tumor progression. Although several mechanisms underlie the etiology of centrosome aberrations in human cancer, upstream regulators are hardly known. Accumulating experimental and clinical evidence points to an important role of estrogens in deregulating centrosome homeostasis and promoting karyotype instability. Here, we will summarize existing literature of how natural and synthetic estrogens might contribute to structural and numerical centrosome defects, genomic instability and human carcinogenesis. Full article

(This article belongs to the Special Issue Comparative Biology of Microtubule Organization in Eukaryotes)

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12 pages, 931 KiB

Open AccessReview

Microtubular TRIM36 E3 Ubiquitin Ligase in Embryonic Development and Spermatogenesis

by Martina Mascaro, Inês Lages and Germana Meroni

Cells 2022, 11(2), 246; https://doi.org/10.3390/cells11020246 - 12 Jan 2022

Cited by 10 | Viewed by 3731

Abstract

TRIM36 is a member of the tripartite motif (TRIM) family of RING-containing proteins, also known as Haprin, which was first discovered for its abundance in testis and found to be implicated in the spermatozoa acrosome reaction. TRIM36 is a microtubule-associated E3 ubiquitin ligase [...] Read more.

TRIM36 is a member of the tripartite motif (TRIM) family of RING-containing proteins, also known as Haprin, which was first discovered for its abundance in testis and found to be implicated in the spermatozoa acrosome reaction. TRIM36 is a microtubule-associated E3 ubiquitin ligase that plays a role in cytoskeletal organization, and according to data gathered in different species, coordinates growth speed and stability, acting on the microtubules’ plus end, and impacting on cell cycle progression. TRIM36 is also crucial for early developmental processes, in Xenopus, where it is needed for dorso-ventral axis formation, but also in humans as bi-allelic mutations in the TRIM36 gene cause a form of severe neural tube closure defect, called anencephaly. Here, we review TRIM36-related mechanisms implicated in such composite physiological and pathological processes. Full article

(This article belongs to the Special Issue Comparative Biology of Microtubule Organization in Eukaryotes)

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26 pages, 1853 KiB

Open AccessReview

The Dictyostelium Centrosome

by Ralph Gräf, Marianne Grafe, Irene Meyer, Kristina Mitic and Valentin Pitzen

Cells 2021, 10(10), 2657; https://doi.org/10.3390/cells10102657 - 5 Oct 2021

Cited by 13 | Viewed by 4753

Abstract

The centrosome of Dictyostelium amoebae contains no centrioles and consists of a cylindrical layered core structure surrounded by a corona harboring microtubule-nucleating γ-tubulin complexes. It is the major centrosomal model beyond animals and yeasts. Proteomics, protein interaction studies by BioID and superresolution microscopy [...] Read more.

The centrosome of Dictyostelium amoebae contains no centrioles and consists of a cylindrical layered core structure surrounded by a corona harboring microtubule-nucleating γ-tubulin complexes. It is the major centrosomal model beyond animals and yeasts. Proteomics, protein interaction studies by BioID and superresolution microscopy methods led to considerable progress in our understanding of the composition, structure and function of this centrosome type. We discuss all currently known components of the Dictyostelium centrosome in comparison to other centrosomes of animals and yeasts. Full article

(This article belongs to the Special Issue Comparative Biology of Microtubule Organization in Eukaryotes)

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28 pages, 3517 KiB

Open AccessReview

Ciliary Dyneins and Dynein Related Ciliopathies

by Dinu Antony, Han G. Brunner and Miriam Schmidts

Cells 2021, 10(8), 1885; https://doi.org/10.3390/cells10081885 - 25 Jul 2021

Cited by 18 | Viewed by 9648

Abstract

Although ubiquitously present, the relevance of cilia for vertebrate development and health has long been underrated. However, the aberration or dysfunction of ciliary structures or components results in a large heterogeneous group of disorders in mammals, termed ciliopathies. The majority of human ciliopathy [...] Read more.

Although ubiquitously present, the relevance of cilia for vertebrate development and health has long been underrated. However, the aberration or dysfunction of ciliary structures or components results in a large heterogeneous group of disorders in mammals, termed ciliopathies. The majority of human ciliopathy cases are caused by malfunction of the ciliary dynein motor activity, powering retrograde intraflagellar transport (enabled by the cytoplasmic dynein-2 complex) or axonemal movement (axonemal dynein complexes). Despite a partially shared evolutionary developmental path and shared ciliary localization, the cytoplasmic dynein-2 and axonemal dynein functions are markedly different: while cytoplasmic dynein-2 complex dysfunction results in an ultra-rare syndromal skeleto-renal phenotype with a high lethality, axonemal dynein dysfunction is associated with a motile cilia dysfunction disorder, primary ciliary dyskinesia (PCD) or Kartagener syndrome, causing recurrent airway infection, degenerative lung disease, laterality defects, and infertility. In this review, we provide an overview of ciliary dynein complex compositions, their functions, clinical disease hallmarks of ciliary dynein disorders, presumed underlying pathomechanisms, and novel developments in the field. Full article

(This article belongs to the Special Issue Comparative Biology of Microtubule Organization in Eukaryotes)

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