Identification of a trafficking motif involved in the stabilization and polarization of P2X receptors
Identification of a trafficking motif involved in the stabilization and polarization of P2X receptors
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DOI：
10.1074/jbc.m403940200
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发表时间：
2004-07-09
影响因子：
4.8
通讯作者：
Rassendren, F
中科院分区：
文献类型：
--
作者：
Chaumont, S;Jiang, LH;Rassendren, F
细胞外 ATP 门控通道（P2X 受体）定义了离子型受体的第三个主要家族，它们广泛表达于神经细胞、肌肉以及内分泌和外分泌腺中。 P2X亚基具有两个跨膜结构域，并且受体被认为是由三个亚基寡聚形成的。我们在 P2X 亚基的细胞质 C 末端发现了一个保守基序，这是其表面表达所必需的；由于快速内化，该基序的突变导致质膜上的受体显着减少。将基序转移到报告蛋白 (CD4) 会增强嵌合体的表面表达，表明该基序可能参与细胞表面 P2X 受体的稳定。在神经元中，突变的 P2X(2) 亚基表现出膜表达减少和轴突分布改变。该基序也存在于其他膜蛋白的细胞内区域，例如一些 G 蛋白偶联受体的第三个细胞内环，表明它可能参与其细胞稳定和极化。
Extracellular ATP-gated channels (P2X receptors) define the third major family of ionotropic receptors, and they are expressed widely in nerve cells, muscles, and endocrine and exocrine glands. P2X subunits have two membrane-spanning domains, and a receptor is thought to be formed by oligomerization of three subunits. We have identified a conserved motif in the cytoplasmic C termini of P2X subunits that is necessary for their surface expression; mutations in this motif result in a marked reduction of the receptors at the plasma membrane because of a rapid internalization. Transfer of the motif to a reporter protein (CD4) enhances the surface expression of the chimera, indicating that this motif is likely involved in the stabilization of P2X receptor at the cell surface. In neurons, mutated P2X(2) subunits showed reduced membrane expression and an altered axodendritic distribution. This motif is also present in intracellular regions of other membrane proteins, such as in the third intracellular loop of some G protein-coupled receptors, suggesting that it might be involve in their cellular stabilization and polarization.