CRMP2 Is Involved in Regulation of Mitochondrial Morphology and Motility in Neurons.
CRMP2 Is Involved in Regulation of Mitochondrial Morphology and Motility in Neurons.
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DOI：
10.3390/cells10102781
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发表时间：
2021-10-17
期刊：
影响因子：
6
通讯作者：
Brustovetsky N
中科院分区：
文献类型：
--
作者：
Brustovetsky T;Khanna R;Brustovetsky N
线粒体形态和运动的调节对神经元至关重要，但确切的机制尚不清楚。在这里，我们表明，这些机制可能涉及到的蛋白质反应介导蛋白2（CRMP 2）。CRMP 2附着于神经元线粒体并结合动力蛋白相关蛋白1（Drp 1）、Miro 2和驱动蛋白1轻链（KLC 1）。用磷酸酶PP 1和PP 2A的抑制剂冈田酸（OA）处理神经元，导致CRMP 2在Thr 509/514、Ser 522和Thr 555处的磷酸化增加，并增强Drp 1在Ser 616处的磷酸化。CRMP 2结合小分子（S）-拉考沙胺（（S）-LCM）阻止了OA诱导的CRMP 2在Thr 509/514和Ser 522磷酸化的增加，但不能阻止Thr 555磷酸化的增加，并且也不能减轻Drp 1磷酸化。CRMP 2磷酸化的增加与CRMP 2与Drp 1、Miro 2和KLC 1结合的减少相关。（S）-LCM挽救了CRMP 2与Drp 1和Miro 2的结合，但不与KLC 1结合。与CRMP 2过度磷酸化平行，OA增加线粒体分裂并抑制线粒体运输。（S）-LCM防止OA诱导的线粒体形态和运动性的改变。用小干扰RNA（siRNA）缺失CRMP 2导致线粒体分裂增加和线粒体运输减少。总之，我们的数据表明，CRMP 2的表达水平和磷酸化状态参与调节神经元线粒体的形态和运动。
Regulation of mitochondrial morphology and motility is critical for neurons, but the exact mechanisms are unclear. Here, we demonstrate that these mechanisms may involve collapsin response mediator protein 2 (CRMP2). CRMP2 is attached to neuronal mitochondria and binds to dynamin-related protein 1 (Drp1), Miro 2, and Kinesin 1 light chain (KLC1). Treating neurons with okadaic acid (OA), an inhibitor of phosphatases PP1 and PP2A, resulted in increased CRMP2 phosphorylation at Thr509/514, Ser522, and Thr555, and augmented Drp1 phosphorylation at Ser616. The CRMP2-binding small molecule (S)-lacosamide ((S)-LCM) prevented an OA-induced increase in CRMP2 phosphorylation at Thr509/514 and Ser522 but not at Thr555, and also failed to alleviate Drp1 phosphorylation. The increased CRMP2 phosphorylation correlated with decreased CRMP2 binding to Drp1, Miro 2, and KLC1. (S)-LCM rescued CRMP2 binding to Drp1 and Miro 2 but not to KLC1. In parallel with CRMP2 hyperphosphorylation, OA increased mitochondrial fission and suppressed mitochondrial traffic. (S)-LCM prevented OA-induced alterations in mitochondrial morphology and motility. Deletion of CRMP2 with a small interfering RNA (siRNA) resulted in increased mitochondrial fission and diminished mitochondrial traffic. Overall, our data suggest that the CRMP2 expression level and phosphorylation state are involved in regulating mitochondrial morphology and motility in neurons.
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影响因子：
3.5
作者：
Chen H;Chan DC
通讯作者：
Chan DC
DOI：
10.1083/jcb.200601067
发表时间：
2006-05-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Glater EE;Megeath LJ;Stowers RS;Schwarz TL
通讯作者：
Schwarz TL
影响因子：
3.4
作者：
Brot, Sebastien;Smaoune, Hinda;Honnorat, Jerome
通讯作者：
Honnorat, Jerome
影响因子：
64.8
作者：
GOSHIMA, Y;NAKAMURA, F;STRITTMATTER, SM
通讯作者：
STRITTMATTER, SM
影响因子：
21.3
作者：
Fukata, Y;Itoh, TJ;Kaibuchi, K
通讯作者：
Kaibuchi, K