title: Src mediates endocytosis of TWIK-related acid-sensitive K+ 1 channels in PC12 cells in response to nerve growth factor.
abstract: TWIK-related acid-sensitive K(+) (TASK) channels produce background K(+) currents. We elucidated that TASK1 channels in rat adrenal medullary cells and PC12 cells are internalized in a clathrin-dependent manner in response to nerve growth factor (NGF). Here, the molecular mechanism for this internalization in PC12 cells was explored. The combination of enzyme inhibitors with tropomyosin receptor kinase A mutants revealed that the internalization was mediated by both phospholipase C and phosphatidylinositol 3-kinase pathways that converge on protein kinase C with the consequent activation of Src, a nonreceptor tyrosine kinase. The NGF-induced endocytosis of TASK1 channels did not occur in the presence of the Src inhibitor or with the expression of a kinase-dead Src mutant. Additionally, NGF induced a transient colocalization of Src with the TASK1 channel, but not the TASK1 mutant, in which tyrosine at 370 was replaced with phenylalanine. This TASK1 mutant showed no increase in tyrosine phosphorylation and markedly diminished internalization in response to NGF. We concluded that NGF induces endocytosis of TASK1 channels via tyrosine phosphorylation in its carboxyl terminus.
authors.affiliation: Department of Cell and Systems Physiology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan.
authors.forename: Hidetada
authors.initials: H
authors.lastname: Matsuoka
authors.affiliation: Department of Cell and Systems Physiology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan minoue@med.uoeh-u.ac.jp.
authors.forename: Masumi
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000818:Animals; D004705:Endocytosis / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D016716:PC12 Cells; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D051381:Rats; D019061:src-Family Kinases / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D020932:Nerve Growth Factor; D019061:src-Family Kinases
keywords: NGF; TASK channel; TrkA; endocytosis; tyrosine phosphorylation