Actin-binding protein α-actinin-1 interacts with the metabotropic glutamate receptor type 5b and modulates the cell surface expression and function of the receptor
Actin-binding protein α-actinin-1 interacts with the metabotropic glutamate receptor type 5b and modulates the cell surface expression and function of the receptor
复制标题
DOI：
10.1074/jbc.m608880200
复制
发表时间：
2007-04-20
影响因子：
4.8
通讯作者：
Ciruela, Francisco
中科院分区：
文献类型：
--
作者：
Cabello, Nuria;Remelli, Rosaria;Ciruela, Francisco
神经递质受体需要支架蛋白来实现膜微区靶向以及调节受体功能。通过酵母双杂交筛选，一种主要的F -肌动蛋白交联蛋白α-辅肌动蛋白-1被鉴定为代谢型谷氨酸受体5b型（mGlu(5b)受体）C末端结构域的结合伴侣。共表达、免疫共沉淀和下拉实验表明，在转染的HEK293细胞和大鼠纹状体中，mGlu(5b)受体与α-辅肌动蛋白-1之间存在紧密且特异性的相互作用。α-辅肌动蛋白-1与mGlu(5b)受体的相互作用调节了该受体的细胞表面表达。这依赖于α-辅肌动蛋白-1与肌动蛋白细胞骨架的结合。此外，α-辅肌动蛋白-1/mGlu(5b)受体的相互作用调节了受体介导的丝裂原活化蛋白激酶途径的激活。总之，这些发现表明存在一种依赖于α-辅肌动蛋白-1的mGlu(5b)受体与肌动蛋白细胞骨架的关联，这种关联调节受体的细胞表面表达和功能。
Receptors for neurotransmitters require scaffolding proteins for membrane microdomain targeting and for regulating receptor function. Using a yeast two-hybrid screen, alpha-actinin-1, a major F-actin cross-linking protein, was identified as a binding partner for the C-terminal domain of metabotropic glutamate receptor type 5b (mGlu(5b) receptor). Co-expression, co-immunoprecipitation, and pull-down experiments showed a close and specific interaction between mGlu(5b) receptor and alpha-actinin-1 in both transfected HEK293 cells and rat striatum. The interaction of alpha-actinin-1 with mGlu(5b) receptor modulated the cell surface expression of the receptor. This was dependent on the binding of alpha-actinin-1 to the actin cytoskeleton. In addition, the alpha-actinin-1/mGlu(5b) receptor interaction regulated receptor-mediated activation of the mitogen-activated protein kinase pathway. Together, these findings indicate that there is an alpha-actinin-1-dependent mGlu(5b) receptor association with the actin cytoskeleton modulating receptor cell surface expression and functioning.