SNAREing Voltage-Gated K+ and ATP-Sensitive K+ Channels: Tuning {beta}-Cell Excitability with Syntaxin-1A and Other Exocytotic Proteins

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Title:	SNAREing Voltage-Gated K+ and ATP-Sensitive K+ Channels: Tuning {beta}-Cell Excitability with Syntaxin-1A and Other Exocytotic Proteins
Authors:	梁育民;(Edwin P. Kwan);(Betty Ng);(Youhou Kang);(Herbert Y. Gaisano)
Contributors:	醫學院醫學系學士班生理學科
Date:	2007-10
Issue Date:	2009-08-19 17:23:09 (UTC+8)
Abstract:	The three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, syntaxin, SNAP25 (synaptosome-associated protein of 25 kDa), and synaptobrevin, constitute the minimal machinery for exocytosis in secretory cells such as neurons and neuroendocrine cells by forming a series of complexes prior to and during vesicle fusion. It was subsequently found that these SNARE proteins not only participate in vesicle fusion, but also tether with voltage-dependent Ca2+ channels to form an excitosome that precisely regulates calcium entry at the site of exocytosis. In pancreatic islet ß-cells, ATP-sensitive K+ (KATP) channel closure by high ATP concentration leads to membrane depolarization, voltage-dependent Ca2+ channel opening, and insulin secretion, whereas subsequent opening of voltage-gated K+ (Kv) channels repolarizes the cell to terminate exocytosis. We have obtained evidence that syntaxin-1A physically interacts with Kv2.1 (the predominant Kv in ß-cells) and the sulfonylurea receptor subunit of ß-cell KATP channel to modify their gating behaviors. A model has proposed that the conformational changes of syntaxin-1A during exocytosis induce distinct functional modulations of KATP and Kv2.1 channels in a manner that optimally regulates cell excitability and insulin secretion. Other proteins involved in exocytosis, such as Munc-13, tomosyn, rab3a-interacting molecule, and guanyl nucleotide exchange factor II, have also been implicated in direct or indirect regulation of ß-cell ion channel activities and excitability. This review discusses this interesting aspect that exocytotic proteins not only promote secretion per se, but also fine-tune ß-cell excitability via modulation of ion channel gating.
Relation:	ENDOCRINE REVIEWS 28(6):653~663
Appears in Collections:	[School of Medicine] Journal articles

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