2. Academic Validation
  3. CCM-3/STRIPAK promotes seamless tube extension through endocytic recycling

CCM-3/STRIPAK promotes seamless tube extension through endocytic recycling

  • Nat Commun. 2015 Mar 6:6:6449. doi: 10.1038/ncomms7449.
Benjamin Lant 1,  Bin Yu 1,  Marilyn Goudreault 2,  Doug Holmyard 2,  James D R Knight 2,  Peter Xu 3,  Linda Zhao 1,  Kelly Chin 1,  Evan Wallace 4,  Mei Zhen 5,  Anne-Claude Gingras 5,  W Brent Derry 4
Affiliations

Affiliations

  • 1 Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, 686 Bay Street, Toronto, Ontario, Canada M5G 0A4.
  • 2 Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5.
  • 3 Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
  • 4 1] Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, 686 Bay Street, Toronto, Ontario, Canada M5G 0A4 [2] Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
  • 5 1] Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5 [2] Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
PMID: 25743393 DOI: 10.1038/ncomms7449
Abstract

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.

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