RRC ID 53416
著者 Pal S, Lant B, Yu B, Tian R, Tong J, Krieger JR, Moran MF, Gingras AC, Derry WB.
タイトル CCM-3 Promotes C. elegans Germline Development by Regulating Vesicle Trafficking Cytokinesis and Polarity.
ジャーナル Curr Biol
Abstract Cerebral cavernous malformations (CCMs) are vascular defects of the CNS that arise from loss of integrity of the endothelial cells lining blood capillaries, causing leakage of blood into the brain [1]. This results in headaches, seizures, and/or hemorrhagic stroke, depending on the location of the lesion. CCM affects 0.5% of the population and follows an autosomal dominant inheritance pattern caused by mutations in one of the three genes: CCM1 (gene name KRIT1), CCM2 (also known as malcavernin or OSM), and CCM3 (gene name PDCD10) [2, 3], with the earliest onset and most severe prognosis occurring in CCM3 patients [4]. The three CCM genes encode structurally distinct scaffold proteins that function in multiple complexes [5-9]. Using the C. elegans germline as a model of multicellular tube development, we show here that CCM-3 is enriched at the luminal membrane of the germline and the contractile ring of dividing cells in the embryo. Loss of ccm-3 results in defective RAB-11-mediated endocytic recycling, which in turn is necessary for gonadal lumen (rachis) formation, completion of cytokinesis, and localization of cell-surface receptors. CCM-3-mediated localization of anillin and non-muscle myosin to the lateral surfaces of germ cells is required for proper cytoskeletal organization, subsequent oocyte growth, and localization of polarity proteins. Biochemical analysis reveals conservation of the STRIPAK complex and distinct roles for GCK-1 (germinal center kinase III family protein) and striatin/CASH-1 in controlling the localization and function of CCM-3. Taken together, our data establish CCM-3 as a novel regulator of rachis lumenization and polarity establishment during embryogenesis.
巻・号 27(6)
ページ 868-876
公開日 2017-3-20
DOI 10.1016/j.cub.2017.02.028
PII S0960-9822(17)30196-3
PMID 28285997
MeSH Animals Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / physiology* Caenorhabditis elegans / embryology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Cell Polarity / genetics Cell Polarity / physiology* Cytokinesis / genetics Cytokinesis / physiology* Embryonic Development / genetics* Germ Cells / metabolism* Membrane Proteins / genetics Membrane Proteins / physiology* Protein Transport
IF 9.601
引用数 15
リソース情報
線虫 tm2806