Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites
Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites
复制标题
DOI：
10.1038/nature743
复制
发表时间：
2002-05-02
期刊：
影响因子：
64.8
通讯作者：
Hirokawa, N
中科院分区：
文献类型：
--
作者：
Setou, M;Seog, DH;Hirokawa, N
在细胞中，分子马达在分子的极化分选中起作用，尽管马达的操纵机制仍然难以捉摸（1）。在神经元中，驱动蛋白马达（2）进行囊泡运输，例如将突触囊泡组分运输到轴突（3）和将神经递质受体运输到树突（4），这表明囊泡可能必须驱动马达才能正确方向。在这里，我们表明，AMPA（α-氨基-3-羟基-5-甲基异恶唑-4-丙酸酯）受体亚基-GluR 2相互作用蛋白（GRIP 1）-可以直接相互作用，并引导驱动蛋白重链树突作为电机的AMPA受体。如所预期的，如果该复合物是功能性的，则小鼠驱动蛋白重链的基因靶向和显性阴性实验均显示GRIP 1的异常定位。此外，GRIP 1的驱动蛋白结合结构域的表达导致内源性驱动蛋白主要在体树突区域的积累。这种模式与驱动蛋白结合支架蛋白JSAP 1（JNK/SAPK相关蛋白1，也称为Mapk 8ip 3）的过表达所产生的模式不同，后者主要发生在体轴突区域。这些结果表明，直接结合的蛋白质可以决定一个马达蛋白的交通方向。
In cells, molecular motors operate in polarized sorting of molecules, although the steering mechanisms of motors remain elusive(1). In neurons, the kinesin motor(2) conducts vesicular transport such as the transport of synaptic vesicle components to axons(3) and of neurotransmitter receptors to dendrites(4), indicating that vesicles may have to drive the motor for the direction to be correct. Here we show that an AMPA (alpha-amino-3-hydroxy-5- methylisoxazole-4-propionate) receptor subunit-GluR2-interacting protein (GRIP1)-can directly interact and steer kinesin heavy chains to dendrites as a motor for AMPA receptors. As would be expected if this complex is functional, both gene targeting and dominant negative experiments of heavy chains of mouse kinesin showed abnormal localization of GRIP1. Moreover, expression of the kinesin-binding domain of GRIP1 resulted in accumulation of the endogenous kinesin predominantly in the somatodendritic area. This pattern was different from that generated by the overexpression of the kinesin-binding scaffold protein JSAP1 (JNK/SAPK-associated protein-1, also known as Mapk8ip3), which occurred predominantly in the somatoaxon area. These results indicate that directly binding proteins can determine the traffic direction of a motor protein.