Molecular characterization and localization of the RIC-3 protein, an effector of nicotinic acetylcholine receptor expression
Molecular characterization and localization of the RIC-3 protein, an effector of nicotinic acetylcholine receptor expression
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DOI：
10.1111/j.1471-4159.2007.05169.x
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发表时间：
2008-05-01
影响因子：
4.7
通讯作者：
Criado, Manuel
中科院分区：
文献类型：
--
作者：
Castelan, Francisco;Castillo, Mar;Criado, Manuel
RIC-3 蛋白充当乙酰胆碱烟碱受体 (nAChR) 表达的调节剂。在非洲爪蟾卵母细胞中，人 RIC-3 (hRIC-3) 蛋白增强 α7 受体的表达并消除 α4β2 受体的表达。 hRIC-3 的体外翻译证明了其膜插入，但未证明其作为其第一个跨膜结构域 (TMD) 信号肽的作用。当 hRIC-3 的 TMD 被替换时，其对 nAChR 表达的影响减弱。 TMD 之间一定的接头长度对于 α 7 表达增强也是必需的，但对于 α 4 β 2 抑制则不需要。 α 7 受体稳态水平增加、转运促进和受体内化减少的组合似乎是 hRIC-3 诱导的 α 7 膜表达增加的原因。针对 hRIC-3 的抗体显示其在 SH-SY5Y 和 PC12 细胞中的表达及其分化诱导。免疫组织化学证明，大鼠大脑中 RIC-3 的存在通常位于发现 α7 nAChR 的地方。
The RIC-3 protein acts as a regulator of acetylcholine nicotinic receptor (nAChR) expression. In Xenopus laevis oocytes the human RIC-3 (hRIC-3) protein enhances expression of alpha 7 receptors and abolishes expression of alpha 4 beta 2 receptors. In vitro translation of hRIC-3 evidenced its membrane insertion but not the role as signal peptide of its first transmembrane domain (TMD). When the TMDs of hRIC-3 were substituted, its effects on nAChR expression were attenuated. A certain linker length between the TMDs was also needed for alpha 7 expression enhancement but not for alpha 4 beta 2 inhibition. A combination of increased alpha 7 receptor steady state levels, facilitated transport and reduced receptor internalization appears to be responsible for the increase in alpha 7 membrane expression induced by hRIC-3. Antibodies against hRIC-3 showed its expression in SH-SY5Y and PC12 cells and its induction upon differentiation. Immunohistochemistry demonstrated the presence of RIC-3 in rat brain localized, in general, in places where alpha 7 nAChRs were found.