A Sterile 20 Family Kinase and Its Co-factor CCM-3 Regulate Contractile Ring Proteins on Germline Intercellular Bridges

Rehain-Bell, Kathryn; Love, Andrew G.; Werner, Michael; MacLeod, Ian; Yates, John R.; Maddox, Amy Shaub

doi:10.1016/j.cub.2017.01.058

Cited by 43 publications

(75 citation statements)

References 36 publications

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“…However, the dynamics of GCK-1/CCM-3 localization and their interdependence during cytokinesis were unknown. We followed the anaphase localization of fluorescently-tagged GCK-1 and CCM-3 expressed under the control of their own promoters (Pal et al, 2017;Rehain-Bell et al, 2017). Both are present in the cytoplasm and enrich in the cytokinetic ring during anaphase ( Figure 1A and B).…”

Section: Resultsmentioning

confidence: 99%

“…The identification of novel anillin-interacting proteins that limit contractility fit logically with their localization to stable intercellular bridges. However, we and others noted that GCK-1/CCM-3 also enrich on the dynamic, contractile cytokinetic ring in the C. elegans zygote (Pal et al, 2017;Rehain-Bell et al, 2017). Here, we investigated the regulation of contractility in the C. elegans zygote by GCK-1/CCM-3.…”

Section: Introductionmentioning

confidence: 95%

“…Despite over 100 years of study, the mechanisms of cytokinetic ring constriction remain poorly understood. To gain new insights, we identified novel anillin-interacting proteins and found Germinal Center Kinase -1 (GCK-1), a serine/threonine kinase related to budding yeast Ste20 (sterile-20) and the only orthologue of the mammalian germinal center kinase III subfamily in C. elegans which have been implicated in apoptosis, proliferation, polarity and cell motility (Rehain-Bell et al, 2017;Schouest et al, 2009;Yin et al, 2012;Zheng et al, 2010). One well characterized interaction partner of GCK-1 is CCM-3, which is thought to recruit GCK-1 to the STRIPAK complex (Hwang and Pallas, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Together these proteins are thought to regulate endothelial integrity in part by negatively regulating RhoA (Borikova et al, 2010;Richardson et al, 2013;Zheng et al, 2010). We and others characterized the roles of C. elegans GCK-1 and its co-factor Cerebral Cavernous Malformations -3 (CCM-3; collectively, GCK-1/CCM-3) in maintaining structural integrity of the oogenic syncytial germline (Pal et al, 2017;Rehain-Bell et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…GCK-1/CCM-3 promote the stability of the intercellular bridges that connect developing oocytes with a shared cytoplasm by limiting the abundance of proteins that promote contractility (including anillin and NMM-II (NMY-2)) (Pal et al, 2017;Rehain-Bell et al, 2017). We proposed that GCK-1/CCM-3 suppress anillin and NMY-2 localization by inhibiting RhoA, as their vertebrate homologs are known to do (Rehain-Bell et al, 2017;Richardson et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Novel cytokinetic ring components drive negative feedback in cortical contractility

Rehain-Bell

Werner

Doshi

et al. 2019

Preprint

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Actomyosin-driven cortical contractility is a hallmark of many biological processes. While most attention has been given to the positive regulation of contractility, it is becoming increasingly appreciated that contractility is also limited by negative regulation and mechanical brakes. The cytokinetic ring is an actomyosin contractile structure whose assembly and constriction are activated by the small GTPase RhoA. Here we describe the role of two novel cytokinetic ring components GCK-1 and CCM-3 in inhibiting contractility in the cytokinetic ring. GCK-1 and CCM-3 co-localize with essential cytokinetic ring proteins such as active RhoA, the scaffold protein anillin and non-muscle myosin II (NMM-II) during anaphase. GCK-1 and CCM-3 are interdependent for their localization and require active RhoA and anillin but not NMM-II for their recruitment to the cytokinetic furrow. Partial depletion of either GCK-1 or CCM-3 leads to an increase of active RhoA, anillin and NMM-II in the cytokinetic furrow and increased rates of furrow ingression. Furthermore, GCK-1 and CCM-3 localize to actomyosin foci during pulsed contractility of the cortical cytoskeleton during zygote polarization. Depletion of GCK-1 or CCM-3 leads to an increase in both cortical contractility and baseline active RhoA levels. Together, our findings suggest that GCK-1 and CCM-3 limit contractility during zygote polarization and

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Novel cytokinetic ring components drive negative feedback in cortical contractility

Rehain-Bell

Werner

Doshi

et al. 2019

Preprint

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Caenorhabditis elegans septins contribute to the development and structure of the oogenic germline

Perry,

Werner,

Rivenbark

et al. 2023

Cytoskeleton

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Oocytes must be exceptionally large cells in order to support embryonic development. Throughout animal phylogeny, a specialized cell called a syncytium, wherein many nuclei share a continuous cytoplasm, achieves oogenesis. The syncytial nature of germline architecture is key to its function and depends on conserved components of the cortical cytoskeleton. Septins form non‐polar cytoskeletal polymers that associate with membranes. In the syncytial germline of the nematode Caenorhabditis elegans, septins are highly enriched on the cortex and generally required for fertility, but the role of septins in the germline is poorly understood. We report that the C. elegans septins, UNC‐59 and UNC‐61, are important for germline extension during development, the maintenance of its syncytial architecture, and production of oocytes. While much of our findings substantiate the idea that the two C. elegans septins act together, we also found evidence that they have distinct functions. Loss of UNC‐61 perturbed germline extension during germline development, while the loss of UNC‐59 function severely affected germline architecture in adult hermaphrodites. Consultation of clustering results from a large‐scale high‐throughput screen suggested that septins are involved in germ cell proliferation and/or differentiation. In sum, our findings implicate a conserved cytoskeletal component in the complex architecture of a germline syncytium.

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Molecular Biology of CCM

Mládek

Skalický

Beneš

et al. 2020

Cavernomas of the CNS

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A Sterile 20 Family Kinase and Its Co-factor CCM-3 Regulate Contractile Ring Proteins on Germline Intercellular Bridges

Cited by 43 publications

References 36 publications

Novel cytokinetic ring components drive negative feedback in cortical contractility

Novel cytokinetic ring components drive negative feedback in cortical contractility

Caenorhabditis elegans septins contribute to the development and structure of the oogenic germline

Molecular Biology of CCM

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