Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca2+/calmodulin.
Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca2+/calmodulin.
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DOI：
10.1083/jcb.200409157
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发表时间：
2005-08-01
影响因子：
7.8
通讯作者：
Meyer, Tobias
中科院分区：
文献类型：
--
作者：
Fivaz, Marc;Meyer, Tobias
Ras/MAPK通路调节中枢神经系统神经元的突触可塑性和细胞存活。在这里，我们表明，KRas，但不是HRas，急性易位从质膜（PM）的高尔基复合体和早期/回收内体响应神经元的活动。易位是可逆的，并由KRas的多碱异戊二烯基膜靶向基序介导。我们提供的证据表明，KRas易位发生通过螯合的聚异戊二烯基序的钙离子/钙调蛋白（Ca 2 +/CaM）和随后的释放KRas从PM，在一个过程中让人想起GDP的解离底物介导的膜再循环的Rab和Rho GTP酶。KRas易位伴随着其活性的部分细胞内再分布。我们的结论是，聚异戊二烯基序作为Ca 2 +/CaM调节的分子开关，控制PM浓度的KRas和重新分配其活动的内部网站。因此，我们的数据定义了一种新的信号传导机制，差异调节KRas和HRas的定位和活动的神经元。
The Ras/MAPK pathway regulates synaptic plasticity and cell survival in neurons of the central nervous system. Here, we show that KRas, but not HRas, acutely translocates from the plasma membrane (PM) to the Golgi complex and early/recycling endosomes in response to neuronal activity. Translocation is reversible and mediated by the polybasic-prenyl membrane targeting motif of KRas. We provide evidence that KRas translocation occurs through sequestration of the polybasic-prenyl motif by Ca2+/calmodulin (Ca2+/CaM) and subsequent release of KRas from the PM, in a process reminiscent of GDP dissociation inhibitor–mediated membrane recycling of Rab and Rho GTPases. KRas translocation was accompanied by partial intracellular redistribution of its activity. We conclude that the polybasic-prenyl motif acts as a Ca2+/CaM-regulated molecular switch that controls PM concentration of KRas and redistributes its activity to internal sites. Our data thus define a novel signaling mechanism that differentially regulates KRas and HRas localization and activity in neurons.