Dual role of the RIC-3 protein in trafficking of serotonin and nicotinic acetylcholine receptors
Dual role of the RIC-3 protein in trafficking of serotonin and nicotinic acetylcholine receptors
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DOI：
10.1074/jbc.m503746200
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发表时间：
2005-07-22
影响因子：
4.8
通讯作者：
Criado, M
中科院分区：
文献类型：
--
作者：
Castillo, M;Mulet, J;Criado, M
在秀丽隐杆线虫中，ric3基因是烟碱乙酰胆碱受体成熟所必需的。RIC-3的人类同源物hRIC-3增强了非洲爪蟾卵母细胞中α - 7烟碱受体的表达，而完全消除α - 4 - β - 2烟碱受体和5-HT3血清素能受体的表达。hRIC-3包含两个跨膜片段的n端区域和c端区域都需要这些差异效应。hRIC-3通过阻碍成熟受体向细胞膜的输出来抑制受体的表达。通过使用由α 7和5-HT3受体组成的嵌合蛋白，我们已经证明靠近第一个跨膜受体片段的细胞外异亮氨酸的存在是hRIC-3诱导的运输阻滞的原因。α - 7受体表达的增强至少在两个层面上发生：通过增加成熟受体的数量和促进其向膜的运输。存在于α 7亚基的大细胞质区域的假定的两性螺旋的某些氨基酸是这些作用所必需的。因此，hRIC-3可以在不同水平上作为受体表达的特异性调节剂。
The ric-3 gene is required for maturation of nicotinic acetylcholine receptors in Caenorhabditis elegans. The human homolog of RIC-3, hRIC-3, enhances expression of alpha 7 nicotinic receptors in Xenopus laevis oocytes, whereas it totally abolishes expression of alpha 4 beta 2 nicotinic and 5-HT3 serotonergic receptors. Both the N-terminal region of hRIC-3, which contains two transmembrane segments, and the C-terminal region are needed for these differential effects. hRIC-3 inhibits receptor expression by hindering export of mature receptors to the cell membrane. By using chimeric proteins made of alpha 7 and 5-HT3 receptors, we have shown that the presence of an extracellular isoleucine close to the first transmembrane receptor fragment is responsible for the transport arrest induced by hRIC-3. Enhancement of alpha 7 receptor expression occurs, at least, at two levels: by increasing the number of mature receptors and facilitating its transport to the membrane. Certain amino acids of a putative amphipathic helix present at the large cytoplasmic region of the alpha 7 subunit are required for these actions. Therefore, hRIC-3 can act as a specific regulator of receptor expression at different levels.