title: Compensatory endocytosis in bladder umbrella cells occurs through an integrin-regulated and RhoA- and dynamin-dependent pathway.
abstract: Compensatory endocytosis (CE) ensures recycling of membrane components and maintenance of plasma membrane size; however, the mechanisms, regulation, and physiological functions of clathrin-independent modes of CE are poorly understood. CE was studied in umbrella cells, which undergo regulated exocytosis of subapical discoidal/fusiform vesicles (DFV) during bladder filling, and may then replenish the pool of DFV by internalizing apical membrane during voiding. We found that voiding-stimulated CE, which depended on beta(1) integrin-associated signalling pathways, occurred by a dynamin-, actin-, and RhoA-regulated mechanism and was independent of caveolins, clathrin, and flotillin. Internalized apical membrane and fluid were initially found in ZO-1-positive vesicles, which were distinct from DFV, classical early endosomes, or the Golgi, and subsequently in lysosomes. We conclude that clathrin-independent CE in umbrella cells functions to recover membrane during voiding, is integrin regulated, occurs by a RhoA- and dynamin-dependent pathway, and terminates in degradation and not recapture of membrane in DFV.
authors.affiliation: Department of Medicine, Laboratory of Epithelial Cell Biology and Renal-Electrolyte Division, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Puneet
authors.initials: P
authors.lastname: Khandelwal
authors.forename: Wily G
authors.initials: WG
authors.lastname: Ruiz
authors.forename: Gerard
authors.initials: G
authors.lastname: Apodaca
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D022461:Caveolins / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism*; D004705:Endocytosis; D019012:Integrin beta1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D011817:Rabbits; D022161:Transport Vesicles / Q000502:physiology; D001743:Urinary Bladder / Q000502:physiology*; D019459:Urothelium / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D022461:Caveolins; D002966:Clathrin; D019012:Integrin beta1; D008565:Membrane Proteins; C106354:flotillins; D020742:rhoA GTP-Binding Protein; D034281:Dynamins
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