Presentation/Session Information

Session Information

Session Title: Cytoskeleton and Trafficking Session Type: Parallel
Session Location: Northwest Auditorium Session Time: Fri, Jun 26 8:30AM - 11:30AM

Presentation Information

Program Number: 114 Presentation Time: 8:54AM - 9:06AM

Presentation Content

CCM-3/STRIPAK promotes excretory canal extension through endocytic recycling.Benjamin Lant. The Hospital for Sick Children, Toronto, Ontar

Cerebral cavernous malformation (CCM) is a disease of the neurovasculature, which can lead to seizure and stroke. It is caused by mutation in one of three members of this family of genes (CCM1/2/3). These mutations can be as common as 1 in 200 in some populations, and can arise hereditarily or sporadically. Of the three genes, mutations in CCM3 cause the earliest onset and have the most severe prognosis. 

We have discovered that CCM-3 (the C. elegans homolog of human CCM3), independent of KRI-1 (the C. elegans CCM1 homolog), regulates vascular tube growth in the worm model. Mutation of ccm-3 causes severe truncation and extensive lumen defects within the excretory canal, which resemble the cavernous malformations in patients. We have shown that CCM-3 localizes to the apical membrane, and in conjunction with GCK-1 and members of the striatin interacting phosphatase and kinase (STRIPAK) complex, affects actin, CDC-42 signalling, Golgi stability, and endocytic recycling. This suggests the first in vivo role for CCM3/STRIPAK. TEM imaging further reveals that loss of ccm-3 affects the co-ordinated building of basolateral and apical membranes by causing improper aggregations of canalicular vesicles; which in turn form ectopic lumen (cysts). These novel roles for CCM-3/STRIPAK in regulating tube extension may begin to explain the severity of CCM3 mutations in patients.




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