Target Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein Receptors (t-SNAREs) Differently Regulate Activation and Inactivation Gating of Kv2.2 and Kv2.1: Implications on Pancreatic Islet Cell Kv Channels
Target Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein Receptors (t-SNAREs) Differently Regulate Activation and Inactivation Gating of Kv2.2 and Kv2.1: Implications on Pancreatic Islet Cell Kv Channels
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目标可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体 (t-SNARE) 不同地调节 Kv2.2 和 Kv2.1 的激活和失活门控：对胰岛细胞 Kv 通道的影响
DOI：
10.1124/mol.105.021717
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发表时间：
2006
影响因子：
3.6
通讯作者：
I. Lotan
中科院分区：
文献类型：
--
作者：
Tami Wolf;I. Michaelevski;L. Sheu;H. Gaisano;D. Chikvashvili;I. Lotan
我们假设胞吐可溶性N-乙基马来酰亚胺敏感因子附着蛋白（SNAP）受体（SNARE）复合物的质膜蛋白组分，突触融合蛋白1A和SNAP-25，明显调节差异分布的不同电压门控K+（KV）通道。神经内分泌胰岛细胞（α、β、δ）均含有突触融合蛋白1A和SNAP-25。然而，使用免疫组织化学，我们发现不同的胰岛细胞含有不同的优势Kv通道，包括β细胞中的Kv2.1和α和δ细胞中的Kv2.2，其与SNARE蛋白的相互作用将分别调节胰岛素、胰高血糖素和生长抑素的分泌。因此，我们研究了syntaxin 1A和SNAP-25对这两个通道的调节。我们已经表明，Kv2.1与突触融合蛋白1A和SNAP-25相互作用，并根据在卵母细胞中的研究，提出了两种不同的模式的相互作用的突触融合蛋白1A和复杂的突触融合蛋白1A/SNAP-25与通道的C末端的模型。在这里，我们的特点是相互作用的syntaxin 1A和SNAP-25与Kv2.2是高度同源的Kv2.1，除了C-末端。在卵母细胞中比较Kv2.2和Kv2.1之间的双电极电压钳分析显示，Kv2.2仅与突触融合蛋白1A相互作用，与Kv2.1相反，它不与突触融合蛋白1A/SNAP-25复合物相互作用，因此对复合物的组装/分解状态不敏感。SNARE对这些密切相关的通道的不同调节可能归因于它们C末端的差异。连同这些通道在胰岛细胞中的差异分布，它们的独特调节表明，糖尿病中记录的胰岛SNARE水平的显著下调可能以不同的方式扭曲胰岛细胞离子通道和分泌反应，最终导致异常的葡萄糖稳态。
We have hypothesized that the plasma membrane protein components of the exocytotic soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) complex, syntaxin 1A and SNAP-25, distinctly regulate different voltage-gated K+ (Kv) channels that are differentially distributed. Neuroendocrine islet cells (α, β, δ) uniformly contain both syntaxin 1A and SNAP-25. However, using immunohistochemistry, we show that the different pancreatic islet cells contain distinct dominant Kv channels, including Kv2.1 in β cells and Kv2.2 in α and δ cells, whose interactions with the SNARE proteins would, respectively regulate insulin, glucagon and somatostatin secretion. We therefore examined the regulation by syntaxin 1A and SNAP-25 of these two channels. We have shown that Kv2.1 interacts with syntaxin 1A and SNAP-25 and, based on studies in oocytes, suggested a model of two distinct modes of interaction of syntaxin 1A and the complex syntaxin 1A/SNAP-25 with the C terminus of the channel. Here, we characterized the interactions of syntaxin 1A and SNAP-25 with Kv2.2 which is highly homologous to Kv2.1, except for the C-terminus. Comparative two-electrode voltage clamp analysis in oocytes between Kv2.2 and Kv2.1 shows that Kv2.2 interacts only with syntaxin 1A and, in contrast to Kv2.1, it does not interact with the syntaxin 1A/SNAP-25 complex and hence is not sensitive to the assembly/disassembly state of the complex. The distinct regulation of these closely related channels by SNAREs may be attributed to differences in their C termini. Together with the differential distribution of these channels among islet cells, their distinct regulation suggests that the documented profound down-regulation of islet SNARE levels in diabetes could distort islet cell ion channels and secretory responses in different ways, ultimately contributing to the abnormal glucose homeostasis.
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影响因子：
4.8
作者：
M. Wheeler;L. Sheu;M. Ghai;A. Bouquillon;G. Grondin;U. Weller;A. Beaudoin;M. Bennett;W. Trimble;H. Gaisano
通讯作者：
M. Wheeler;L. Sheu;M. Ghai;A. Bouquillon;G. Grondin;U. Weller;A. Beaudoin;M. Bennett;W. Trimble;H. Gaisano
影响因子：
4.8
作者：
Gaisano, HY;Ostenson, CG;Efendic, S
通讯作者：
Efendic, S
影响因子：
3.7
作者：
Honer, WG;Falkai, P;Trimble, WS
通讯作者：
Trimble, WS
Ca(2) 流入和cAMP 升高克服了肉毒杆菌毒素A 但不能克服破伤风毒素对胰岛素胞吐作用的抑制。
DOI：
10.1152/ajpcell.2001.281.3.c740
发表时间：
2001
期刊：
American journal of physiology. Cell physiology
影响因子：
--
作者：
Huang,X;Kang,YH;Pasyk,EA;Sheu,L;Wheeler,MB;Trimble,WS;Salapatek,A;Gaisano,HY
通讯作者：
Gaisano,HY
影响因子：
--
作者：
MacDonald, PE;Wang, GT;Gaisano, HY
通讯作者：
Gaisano, HY