Matches in SemOpenAlex for { <https://semopenalex.org/work/W2884072849> ?p ?o ?g. }
- W2884072849 abstract "Endothelial integrity relies on a mechanical crosstalk between intercellular and cell-matrix interactions. This cross-talk is compromised in hemorrhagic vascular lesions of patients carrying loss-of-function mutations in CCM genes. RhoA/ROCK-dependent cytoskeletal remodeling is central to the disease as it causes unbalanced cell adhesion towards increased cell-extracellular matrix adhesions and destabilized cell-cell junctions. Our study reveals that CCM proteins directly orchestrate ROCK1 and ROCK2 complementary roles on the mechanics of the endothelium. CCM proteins act as a scaffold promoting ROCK2 interactions with VE-cadherin and limiting ROCK1 kinase activity. Loss of CCM1 produces excessive ROCK1-dependent actin stress fibers and destabilizes intercellular junctions. Silencing of ROCK1 but not ROCK2 restores the adhesive and mechanical homeostasis of CCM1/2-depleted endothelial monolayers and rescues cardiovascular defects of ccm1 mutant zebrafish embryos. Conversely, knocking down of Rock2 but not Rock1 in WT zebrafish embryos generates defects reminiscent of the ccm1 mutant phenotypes. Our study uncovers the role of the CCM complex in controlling ROCK1 and ROCK2 to preserve endothelial integrity and drive heart morphogenesis. Moreover, it identifies solely the ROCK1 isoform as therapeutic target for the CCM disease." @default.
- W2884072849 created "2018-08-03" @default.
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- W2884072849 date "2018-01-01" @default.
- W2884072849 modified "2023-10-10" @default.
- W2884072849 title "Cerebral Cavernous Malformation 1/2 complex controls ROCK1 and ROCK2 complementary functions for endothelial integrity" @default.
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- W2884072849 cites W1906023659 @default.
- W2884072849 cites W1944253530 @default.
- W2884072849 cites W1956254703 @default.
- W2884072849 cites W1967147410 @default.
- W2884072849 cites W1967489328 @default.
- W2884072849 cites W1969564302 @default.
- W2884072849 cites W1982149574 @default.
- W2884072849 cites W1985356361 @default.
- W2884072849 cites W1994825452 @default.
- W2884072849 cites W2004220217 @default.
- W2884072849 cites W2004248277 @default.
- W2884072849 cites W2007995027 @default.
- W2884072849 cites W2008065145 @default.
- W2884072849 cites W2012278629 @default.
- W2884072849 cites W2016519574 @default.
- W2884072849 cites W2026261537 @default.
- W2884072849 cites W2027052842 @default.
- W2884072849 cites W2050612706 @default.
- W2884072849 cites W2052103073 @default.
- W2884072849 cites W2054971583 @default.
- W2884072849 cites W2058599028 @default.
- W2884072849 cites W2061600983 @default.
- W2884072849 cites W2065240196 @default.
- W2884072849 cites W2072890764 @default.
- W2884072849 cites W2086523714 @default.
- W2884072849 cites W2091657419 @default.
- W2884072849 cites W2095035711 @default.
- W2884072849 cites W2098410928 @default.
- W2884072849 cites W2099094107 @default.
- W2884072849 cites W2099249565 @default.
- W2884072849 cites W2099824652 @default.
- W2884072849 cites W2104850611 @default.
- W2884072849 cites W2105496477 @default.
- W2884072849 cites W2107798346 @default.
- W2884072849 cites W2111245936 @default.
- W2884072849 cites W2112668385 @default.
- W2884072849 cites W2112912820 @default.
- W2884072849 cites W2117038928 @default.
- W2884072849 cites W2123892536 @default.
- W2884072849 cites W2127213821 @default.
- W2884072849 cites W2130136843 @default.
- W2884072849 cites W2131284305 @default.
- W2884072849 cites W2137353907 @default.
- W2884072849 cites W2145518607 @default.
- W2884072849 cites W2146893645 @default.
- W2884072849 cites W2147327763 @default.
- W2884072849 cites W2148335222 @default.
- W2884072849 cites W2149179723 @default.
- W2884072849 cites W2157056295 @default.
- W2884072849 cites W2158861165 @default.
- W2884072849 cites W2163858320 @default.
- W2884072849 cites W2169001927 @default.
- W2884072849 cites W2171365654 @default.
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- W2884072849 cites W2254262262 @default.
- W2884072849 cites W2260093447 @default.
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- W2884072849 doi "https://doi.org/10.1242/jcs.216093" @default.
- W2884072849 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30030370" @default.
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