title: Caveolins bind to (Na+, K+)/H+ exchanger NHE7 by a novel binding module.
abstract: NHE7 was identified as the first mammalian organelle-membrane type (Na+, K+)/H+ exchanger that may contribute to the ion homeostasis in the trans-Golgi network (TGN) and endosomes. Here we show that caveolins directly bind to the C-terminal extension of NHE7 by an unconventional binding-module. NHE7 is partly associated with caveolae/lipid raft fractions, and heterologous expression of caveolin dominant-negative mutants as well as cholesterol depriving drugs diminished such associations. In contrast to the wild type NHE7, a deletion mutant lacking the C-terminal extension was predominantly detected in non-caveolae/lipid rafts. We further show that a small fraction of NHE7 is targeted to the cell surface and subsequently internalized. Endocytosis of NHE7 was efficiently inhibited by pharmacological maneuvers that block clathrin-dependent endocytosis, whereas dominant-negative caveolin mutants or methyl beta-cyclodextrin did not affect NHE7-internalization. Thus, NHE7 associates with both caveolae/lipid rafts and non-caveolae/lipid raft, and the two pools likely exhibit separate dynamics.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, Canada.
authors.forename: Paulo J C
authors.initials: PJ
authors.lastname: Lin
authors.forename: Warren P
authors.initials: WP
authors.lastname: Williams
authors.forename: Jasmina
authors.initials: J
authors.lastname: Kobiljski
authors.forename: Masayuki
authors.initials: M
authors.lastname: Numata
mesh_terms: D000818:Animals; D016466:CHO Cells; D021941:Caveolae / Q000378:metabolism; D022461:Caveolins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002966:Clathrin / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D003600:Cytosol / Q000737:chemistry; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D022461:Caveolins; D002966:Clathrin; D017923:Sodium-Hydrogen Exchangers