title: A Sterile 20 Family Kinase and Its Co-factor CCM-3 Regulate Contractile Ring Proteins on Germline Intercellular Bridges.
abstract: Germ cells in most animals are connected by intercellular bridges, actin-based rings that form stable cytoplasmic connections between cells promoting communication and coordination [1]. Moreover, these connections are required for fertility [1, 2]. Intercellular bridges are proposed to arise from stabilization of the cytokinetic ring during incomplete cytokinesis [1]. Paradoxically, proteins that promote closure of cytokinetic rings are enriched on stably open intercellular bridges [1, 3, 4]. Given this inconsistency, the mechanism of intercellular bridge stabilization is unclear. Here, we used the C. elegans germline as a model for identifying molecular mechanisms regulating intercellular bridges. We report that bridges are actually highly dynamic, changing size at precise times during germ cell development. We focused on the regulation of bridge stability by anillins, key regulators of cytokinetic rings and cytoplasmic bridges [1, 4-7]. We identified GCK-1, a conserved serine/threonine kinase [8], as a putative novel anillin interactor. GCK-1 works together with CCM-3, a known binding partner [9], to promote intercellular bridge stability and limit localization of both canonical anillin and non-muscle myosin II (NMM-II) to intercellular bridges. Additionally, we found that a shorter anillin, known to stabilize bridges [4, 7], also regulates NMM-II levels at bridges. Consistent with these results, negative regulators of NMM-II stabilize intercellular bridges in the Drosophila egg chamber [10, 11]. Together with our findings, this suggests that tuning of myosin levels is a conserved mechanism for the stabilization of intercellular bridges that can occur by diverse molecular mechanisms.
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Curriculum in Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Rehain-Bell
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Love
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Werner
authors.affiliation: The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: MacLeod
authors.affiliation: The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Curriculum in Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: asm@unc.edu.
authors.forename: Amy Shaub
authors.initials: AS
authors.lastname: Maddox
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism; D048749:Cytokinesis; D005854:Germ Cells / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C502566:ANI-1 protein, C elegans; D051017:Apoptosis Regulatory Proteins; C000627825:CCM-3 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D003285:Contractile Proteins; C546116:GCK-1 protein, C elegans; D008565:Membrane Proteins; D008840:Microfilament Proteins
keywords: C. elegans; CCM-3; GCK III; GCK-1; anillin; cytokinesis; intercellular bridge; rachis