SUMOylation alters CRMP2 regulation of calcium influx in sensory neurons
SUMOylation alters CRMP2 regulation of calcium influx in sensory neurons
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DOI：
10.4161/chan.24224
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发表时间：
2013-05-01
期刊：
影响因子：
3.3
通讯作者：
Khanna, Rajesh
中科院分区：
文献类型：
--
作者：
Ju, Weina;Li, Qi;Khanna, Rajesh
轴突/树突特化介导蛋白2（CRMP 2）双向调节N型电压门控钙通道（CaV2.2）。在这里，我们证明了小泛素样修饰（SUMO）蛋白修饰CRMP 2通过SUMO E2结合酶Ubc 9在体内。CRMP 2中SUMO缀合位点KMD（K374 A/M375 A/D376 A; CRMP 2（AAA））的去除导致SUMO化CRMP 2的损失，而不损害神经突分支，这是CRMP 2功能的典型标志。增加SUMO化水平与感觉神经元中的钙内流呈负相关。通过SUMO蛋白酶SENP 1和SENP 2的CRMP 2去SUMO化使钙内流相对于CRMP 2（AAA）突变体中的钙内流正常化。因此，我们的研究结果确定了CRMP 2/CaV2.2信号通路中SUMO修饰的新作用。
The axon/dendrite specification collapsin response mediator protein 2 (CRMP2) bidirectionally modulates N-type voltage-gated Ca2+ channels (CaV2.2). Here we demonstrate that small ubiquitin-like modifier (SUMO) protein modifies CRMP2 via the SUMO E2-conjugating enzyme Ubc9 in vivo. Removal of a SUMO conjugation site KMD in CRMP2 (K374A/M375A/D376A; CRMP2(AAA)) resulted in loss of SUMOylated CRMP2 without compromising neurite branching, a canonical hallmark of CRMP2 function. Increasing SUMOylation levels correlated inversely with calcium influx in sensory neurons. CRMP2 deSUMOylation by SUMO proteases SENP1 and SENP2 normalized calcium influx to those in the CRMP2(AAA) mutant. Thus, our results identify a novel role for SUMO modification in CRMP2/CaV2.2 signaling pathway.