title: A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells.
abstract: Multiple Rabs are associated with secretory granules/vesicles, but how these GTPases are coordinated to promote regulated exocytosis is not well understood. In bladder umbrella cells a subapical pool of discoidal/fusiform-shaped vesicles (DFVs) undergoes Rab11a-dependent regulated exocytosis in response to bladder filling. We show that Rab11a-associated vesicles are enmeshed in an apical cytokeratin meshwork and that Rab11a likely acts upstream of Rab8a to promote exocytosis. Surprisingly, expression of Rabin8, a previously described Rab11a effector and guanine nucleotide exchange factor for Rab8, stimulates stretch-induced exocytosis in a manner that is independent of its catalytic activity. Additional studies demonstrate that the unconventional motor protein myosin5B motor (Myo5B) works in association with the Rab8a-Rab11a module to promote exocytosis, possibly by ensuring transit of DFVs through a subapical, cortical actin cytoskeleton before fusion. Our results indicate that Rab11a, Rab8a, and Myo5B function as part of a network to promote stretch-induced exocytosis, and we predict that similarly organized Rab networks will be common to other regulated secretory pathways.
authors: Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Puneet
authors: P
authors: Khandelwal
authors: H Sandeep
authors: HS
authors: Prakasam
authors: Dennis R
authors: DR
authors: Clayton
authors: Wily G
authors: WG
authors: Ruiz
authors: Luciana I
authors: LI
authors: Gallo
authors: Daniel
authors: D
authors: van Roekel
authors: Stefan
authors: S
authors: Lukianov
authors: Johan
authors: J
authors: Peränen
authors: James R
authors: JR
authors: Goldenring
authors: Gerard
authors: G
authors: Apodaca
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D005089:Exocytosis; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D019382:Human Growth Hormone / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013314:Stress, Mechanical; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D049452:Green Fluorescent Proteins; D019382:Human Growth Hormone; D009218:Myosins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C101826:Myo5b protein, rat; C530052:Rab8a protein, rat
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