SNAREing voltage-gated K+ and ATP-sensitive K+ 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 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(2+) channels to form an excitosome that precisely regulates calcium entry at the site of exocytosis. In pancreatic islet beta-cells, ATP-sensitive K(+) (K(ATP)) channel closure by high ATP concentration leads to membrane depolarization, voltage-dependent Ca(2+) 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 beta-cells) and the sulfonylurea receptor subunit of beta-cell K(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(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 beta-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 beta-cell excitability via modulation of ion channel gating.
Leung
Yuk M
YM
Departmnet of Physiology, China Medical University, Taichung 40402, Taiwan. ymleung@mail.cmu.edu.tw
Kwan
Edwin P
EP
Ng
Betty
B
Kang
Youhou
Y
Gaisano
Herbert Y
HY
D000818:Animals; D005089:Exocytosis / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D054086:KATP Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D050600:SNARE Proteins / Q000502:physiology*; D050827:Syntaxin 1 / Q000502:physiology*
D054086:KATP Channels; D024642:Potassium Channels, Voltage-Gated; D050600:SNARE Proteins; D050827:Syntaxin 1