The calcium sensor protein visinin-like protein-1 modulates the surface expression and agonist sensitivity of the α4β2 nicotinic acetylcholine receptor
The calcium sensor protein visinin-like protein-1 modulates the surface expression and agonist sensitivity of the α4β2 nicotinic acetylcholine receptor
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DOI：
10.1074/jbc.m206857200
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发表时间：
2002-11-01
影响因子：
4.8
通讯作者：
Anand, R
中科院分区：
文献类型：
--
作者：
Lin, L;Jeanclos, EM;Anand, R
钙传感器蛋白visinin-like protein-1（VILIP-1）是从脑cDNA酵母双杂交文库中分离得到的，该文库以α 4亚基的大胞质结构域为诱饵。VILIP-1是一种豆蔻酰化的钙传感器蛋白，含有三个功能性钙结合EF-手基序。发现α 4亚基残基302-339对于与VILIP-1的相互作用是必需的。VILIP-1与在tsA 201细胞中表达的洗涤剂溶解的重组α 4 β 2乙酰胆碱受体（AChR）以及与从脑分离的天然α 4 AChR共免疫纯化。VILIP-1与重组α 4 β 2 AChRs的共表达上调了它们的表面表达水平约2倍，并增加了它们对乙酰胆碱的激动剂敏感性约3倍。VILIP-1对重组α 4 β 2 AChR的调节在缺乏肉豆蔻酰化或结合钙能力的VILIP-1突变体中减弱。总的来说，这些结果表明，VILIP-1代表了一种新的α 4 β 2 AChR的调节剂，增加其表面表达水平和激动剂敏感性，以响应细胞内钙水平的变化。
The calcium sensor protein visinin-like protein-1 (VILIP-1) was isolated from a brain cDNA yeast two-hybrid library using the large cytoplasmic domain of the alpha4 subunit as a bait. VILIP-1 is a myristoylated calcium sensor protein that contains three functional calcium binding EF-hand motifs. The alpha4 subunit residues 302-339 were found to be essential for the interaction with VILIP-1. VILIP-1 coimmunopurified with detergent-solubilized recombinant alpha4beta2 acetylcholine receptors (AChRs) expressed in tsA201 cells and with native alpha4 AChRs isolated from brain. Coexpression of VILIP-1 with recombinant alpha4beta2 AChRs up-regulated their surface expression levels similar to2-fold and increased their agonist sensitivity to acetylcholine similar to3-fold. The modulation of the recombinant alpha4beta2 AChRs by VILIP-1 was attenuated in VILIP-1 mutants that lacked the ability to be myristoylated or to bind calcium. Collectively, these results suggest that VILIP-1 represents a novel modulator of alpha4beta2 AChRs that increases their surface expression levels and agonist sensitivity in response to changes in the intracellular levels of calcium.