title: Nerve growth factor-induced endocytosis of TWIK-related acid-sensitive K⁺ 1 channels in adrenal medullary cells and PC12 cells.
abstract: TWIK-related acid-sensitive K(+) (TASK) channels belong to a family of two-pore domain K(+) channels which produce background K(+) currents and are involved in important physiological functions, such as acidosis detection. We have recently elucidated that TASK1-like channels function as a sensor of acidosis in rat adrenal medullary (AM) cells and thus are indispensable for the endocrine function of AM cells. Here, using pharmacological, electrophysiological and biochemical methods, we studied how the expression and localisation of TASK1 channels are regulated in rat AM cells and PC12 cells. PC12 cells were found to express not only TASK1 but also TASK3 channels, and they did not constitute a heterodimer. The exposure of AM cells and PC12 cells to nerve growth factor (NGF) induced endocytosis of TASK1, but not TASK3 channels, in a clathrin-dependent manner. Mutation analysis of the TASK1 channel revealed that the dileucine motif (LL263/264) was involved in at least part of the endocytosis. Plating GFP-TASK1-expressing PC12 cells onto a sheet of fibroblasts, which produced NGF, resulted in the endocytosis of GFP-TASK1 channels. Additionally, the expression of TASK1 channels at the protein and mRNA levels was suppressed in PC12 cells treated with NGF for 2 weeks. These results indicate that NGF suppresses the expression of TASK1 channels in the plasma membrane via not only endocytosis but also the inhibition of gene transcription. Thus, no access to NGF may play a major role for the maintenance of TASK1 channels in the cell membrane in AM cells.
authors: Department of Cell and Systems Physiology, University of Occupational and Environmental Health School of Medicine, Kitakyushu 807-8555, Japan.
authors: Hidetada
authors: H
authors: Matsuoka
authors: Keita
authors: K
authors: Harada
authors: Jun
authors: J
authors: Nakamura
authors: Masumi
authors: M
authors: Inoue
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism*; D020816:Amino Acid Motifs; D000818:Animals; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D055098:Endocrine Cells / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects*; D008297:Male; D009154:Mutation; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: C407082:Kcnk9 protein, rat; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D020932:Nerve Growth Factor
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