| First Author | Lant B | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6449 | PubMed ID | 25743393 |
| Mgi Jnum | J:251997 | Mgi Id | MGI:6107315 |
| Doi | 10.1038/ncomms7449 | Citation | Lant B, et al. (2015) CCM-3/STRIPAK promotes seamless tube extension through endocytic recycling. Nat Commun 6:6449 |
| abstractText | The mechanisms governing apical membrane assembly during biological tube development are poorly understood. Here, we show that extension of the C. elegans excretory canal requires cerebral cavernous malformation 3 (CCM-3), independent of the CCM1 orthologue KRI-1. Loss of ccm-3 causes canal truncations and aggregations of canaliculular vesicles, which form ectopic lumen (cysts). We show that CCM-3 localizes to the apical membrane, and in cooperation with GCK-1 and STRIPAK, promotes CDC-42 signalling, Golgi stability and endocytic recycling. We propose that endocytic recycling is mediated through the CDC-42-binding kinase MRCK-1, which interacts physically with CCM-3-STRIPAK. We further show canal membrane integrity to be dependent on the exocyst complex and the actin cytoskeleton. This work reveals novel in vivo roles of CCM-3.STRIPAK in regulating tube extension and membrane integrity through small GTPase signalling and vesicle dynamics, which may help explain the severity of CCM3 mutations in patients. |
