title: Myosin Ia is required for CFTR brush border membrane trafficking and ion transport in the mouse small intestine.
abstract: In enterocytes of the small intestine, endocytic trafficking of CFTR channels from the brush border membrane (BBM) to the subapical endosomes requires the minus-end motor, myosin VI (Myo6). The subapical localization of Myo6 is dependent on myosin Ia (Myo1a) the major plus-end motor associated with the BBM, suggestive of functional synergy between these two motors. In villus enterocytes of the Myo1a KO mouse small intestine, CFTR accumulated in syntaxin-3 positive subapical endosomes, redistributed to the basolateral domain and was absent from the BBM. In colon, where villi are absent and Myo1a expression is low, CFTR exhibited normal localization to the BBM in the Myo1a KO similar to WT. cAMP-stimulated CFTR anion transport in the small intestine was reduced by 58% in the KO, while anion transport in the colon was comparable to WT. Co-immunoprecipitation confirmed the association of CFTR with Myo1a. These data indicate that Myo1a is an important regulator of CFTR traffic and anion transport in the BBM of villus enterocytes and suggest that Myo1a may power apical CFTR movement into the BBM from subapical endosomes. Alternatively, it may anchor CFTR channels in the BBM of villus enterocytes as was proposed for Myo1a's role in BBM localization of sucrase-isomaltase.
authors.affiliation: Department of Pediatrics/Gastroenterology & Hepatology, Yale University School of Medicine, 333 Cedar Street, FMP 408, P.O. Box 208064, New Haven, CT 06520, USA.
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Kravtsov
authors.forename: Christina
authors.initials: C
authors.lastname: Caputo
authors.forename: Anne
authors.initials: A
authors.lastname: Collaco
authors.forename: Nadia
authors.initials: N
authors.lastname: Hoekstra
authors.forename: Marie E
authors.initials: ME
authors.lastname: Egan
authors.forename: Mark S
authors.initials: MS
authors.lastname: Mooseker
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Ameen
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002712:Chlorides; D003106:Colon / Q000166:cytology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004558:Electric Stimulation; D004705:Endocytosis; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism*; D005089:Exocytosis; D006801:Humans; D007421:Intestine, Small / Q000166:cytology; D017136:Ion Transport; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008871:Microvilli / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D002712:Chlorides; C491827:Myo1a protein, mouse; C089785:myosin VI; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D018995:Myosin Heavy Chains