SNAREing Voltage-Gated K super(+) and ATP-Sensitive K super(+) Channels: Tuning {beta}-Cell Excitability with Syntaxin-1A and Other Exocytotic Proteins
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 s...
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Published in | Endocrine reviews Vol. 28; no. 6; pp. 653 - 663 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
01.10.2007
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Online Access | Get full text |
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Summary: | 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 Ca super(2+) channels to form an excitosome that precisely regulates calcium entry at the site of exocytosis. In pancreatic islet {szligbeta}-cells, ATP-sensitive K super(+) (K sub(ATP)) channel closure by high ATP concentration leads to membrane depolarization, voltage-dependent Ca super(2+) channel opening, and insulin secretion, whereas subsequent opening of voltage-gated K super(+) (Kv) channels repolarizes the cell to terminate exocytosis. We have obtained evidence that syntaxin-1A physically interacts with Kv2.1 (the predominant Kv in {szligbeta}-cells) and the sulfonylurea receptor subunit of {szligbeta}-cell K sub(ATP) channel to modify their gating behaviors. A model has proposed that the conformational changes of syntaxin-1A during exocytosis induce distinct functional modulations of K sub(ATP) 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 {szligbeta}-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 {szligbeta}-cell excitability via modulation of ion channel gating. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
ISSN: | 0163-769X |