title: Cooperative endocytosis of the endosomal SNARE protein syntaxin-8 and the potassium channel TASK-1.
abstract: The endosomal SNARE protein syntaxin-8 interacts with the acid-sensitive potassium channel TASK-1. The functional relevance of this interaction was studied by heterologous expression of these proteins (and mutants thereof) in Xenopus oocytes and in mammalian cell lines. Coexpression of syntaxin-8 caused a fourfold reduction in TASK-1 current, a corresponding reduction in the expression of TASK-1 at the cell surface, and a marked increase in the rate of endocytosis of the channel. TASK-1 and syntaxin-8 colocalized in the early endosomal compartment, as indicated by the endosomal markers 2xFYVE and rab5. The stimulatory effect of the SNARE protein on the endocytosis of the channel was abolished when both an endocytosis signal in TASK-1 and an endocytosis signal in syntaxin-8 were mutated. A syntaxin-8 mutant that cannot assemble with other SNARE proteins had virtually the same effect as wild-type syntaxin-8. Total internal reflection fluorescence microscopy showed formation and endocytosis of vesicles containing fluorescence-tagged clathrin, TASK-1, and/or syntaxin-8. Our results suggest that the unassembled form of syntaxin-8 and the potassium channel TASK-1 are internalized via clathrin-mediated endocytosis in a cooperative manner. This implies that syntaxin-8 regulates the endocytosis of TASK-1. Our study supports the idea that endosomal SNARE proteins can have functions unrelated to membrane fusion.
authors.affiliation: Institute of Physiology and Pathophysiology, Marburg University, 35037 Marburg, Germany jdaut@staff.uni-marburg.de vijay@staff.uni-marburg.de.
authors.forename: Vijay
authors.initials: V
authors.lastname: Renigunta
authors.affiliation: Institute of Physiology and Pathophysiology, Marburg University, 35037 Marburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.affiliation: Institute of Physiology and Pathophysiology, Marburg University, 35037 Marburg, Germany.
authors.forename: Marylou
authors.initials: M
authors.lastname: Zuzarte
authors.affiliation: Institute of Physiology and Pathophysiology, Marburg University, 35037 Marburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kling
authors.affiliation: Institute of Physiology and Pathophysiology, Marburg University, 35037 Marburg, Germany.
authors.forename: Xinle
authors.initials: X
authors.lastname: Zou
authors.affiliation: Institute of Physiology and Pathophysiology, Marburg University, 35037 Marburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Siebert
authors.affiliation: Institute of Physiology and Pathophysiology, Marburg University, 35037 Marburg, Germany.
authors.forename: Maren M
authors.initials: MM
authors.lastname: Limberg
authors.affiliation: Institute of Physiology and Pathophysiology, Marburg University, 35037 Marburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Rinné
authors.affiliation: Institute of Physiology and Pathophysiology, Marburg University, 35037 Marburg, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Decher
authors.affiliation: Institute of Physiology and Pathophysiology, Marburg University, 35037 Marburg, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Schlichthörl
authors.affiliation: Institute of Physiology and Pathophysiology, Marburg University, 35037 Marburg, Germany jdaut@staff.uni-marburg.de vijay@staff.uni-marburg.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Daut
mesh_terms: D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D050765:Qa-SNARE Proteins / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D050765:Qa-SNARE Proteins; C420132:potassium channel subfamily K member 3
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