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• W2140080391 abstract "We have hypothesized that the plasma membrane protein components of the exocytotic soluble <i>N</i>-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." @default.
• W2140080391 created "2016-06-24" @default.
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• W2140080391 date "2006-06-05" @default.
• W2140080391 modified "2023-09-27" @default.
• W2140080391 title "Target Soluble <i>N</i>-Ethylmaleimide-Sensitive Factor Attachment Protein Receptors (<i>t</i>-SNAREs) Differently Regulate Activation and Inactivation Gating of Kv2.2 and Kv2.1: Implications on Pancreatic Islet Cell Kv Channels" @default.
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• W2140080391 doi "https://doi.org/10.1124/mol.105.021717" @default.
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