RRC ID 67783
著者 Swiatecka-Urban A, Talebian L, Kanno E, Moreau-Marquis S, Coutermarsh B, Hansen K, Karlson KH, Barnaby R, Cheney RE, Langford GM, Fukuda M, Stanton BA.
タイトル Myosin Vb is required for trafficking of the cystic fibrosis transmembrane conductance regulator in Rab11a-specific apical recycling endosomes in polarized human airway epithelial cells.
ジャーナル J Biol Chem
Abstract Cystic fibrosis transmembrane conductance regulator (CFTR)-mediated Cl(-) secretion across fluid-transporting epithelia is regulated, in part, by modulating the number of CFTR Cl(-) channels in the plasma membrane by adjusting CFTR endocytosis and recycling. However, the mechanisms that regulate CFTR recycling in airway epithelial cells remain unknown, at least in part, because the recycling itineraries of CFTR in these cells are incompletely understood. In a previous study, we demonstrated that CFTR undergoes trafficking in Rab11a-specific apical recycling endosomes in human airway epithelial cells. Myosin Vb is a plus-end-directed, actin-based mechanoenzyme that facilitates protein trafficking in Rab11a-specific recycling vesicles in several cell model systems. There are no published studies examining the role of myosin Vb in airway epithelial cells. Thus, the goal of this study was to determine whether myosin Vb facilitates CFTR recycling in polarized human airway epithelial cells. Endogenous CFTR formed a complex with endogenous myosin Vb and Rab11a. Silencing myosin Vb by RNA-mediated interference decreased the expression of wild-type CFTR and DeltaF508-CFTR in the apical membrane and decreased CFTR-mediated Cl(-) secretion across polarized human airway epithelial cells. A recombinant tail domain fragment of myosin Vb attenuated the plasma membrane expression of CFTR by arresting CFTR recycling. The dominant-negative effect was dependent on the ability of the myosin Vb tail fragment to interact with Rab11a. Taken together, these data indicate that myosin Vb is required for CFTR recycling in Rab11a-specific apical recycling endosomes in polarized human airway epithelial cells.
巻・号 282(32)
ページ 23725-36
公開日 2007-8-10
DOI 10.1074/jbc.M608531200
PII S0021-9258(20)54588-2
PMID 17462998
MeSH Amino Acid Sequence Cell Line Cystic Fibrosis Transmembrane Conductance Regulator / metabolism* Endocytosis Endosomes / metabolism* Epithelial Cells / cytology* Gene Expression Regulation* Gene Silencing Humans Models, Biological Molecular Sequence Data Myosin Heavy Chains / chemistry Myosin Heavy Chains / physiology* Myosin Type V / chemistry Myosin Type V / physiology* RNA Interference Transfection rab GTP-Binding Proteins / metabolism*
IF 4.238
リソース情報
遺伝子材料 pEF-FLAG-mouse myosin Vb-tail (RDB15286)