Localized role of CRMP1 and CRMP2 in neurite outgrowth and growth cone steering
Localized role of CRMP1 and CRMP2 in neurite outgrowth and growth cone steering
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DOI：
10.1002/dneu.22017
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发表时间：
2012-12-01
影响因子：
3
通讯作者：
Goshima, Yoshio
中科院分区：
文献类型：
--
作者：
Higurashi, Masakazu;Iketani, Masumi;Goshima, Yoshio
折叠蛋白反应介导蛋白 1 (CRMP1) 和 CRMP2 被认为是信号蛋白 3A 等细胞外引导信号的介导者，有助于轴突寻路过程中的细胞骨架重组。迄今为止，CRMP1 和 CRMP2 如何集中调节生长锥中的轴突寻路尚未阐明。为了描述这些 CRMP 的局部功能，我们进行了微尺度发色团辅助光灭活（micro-CALI），这使得能够以高空间和时间分辨率研究局部分子功能。神经突轴中 CRMP1 或 CRMP2 的失活会导致神经突生长受阻。生长锥中央区域中 CRMP2 的微 CALI 持续抑制神经突生长，而同一区域中 CRMP1 的微 CALI 引起显着的片状足回缩，随后延迟神经突生长。 CRMP1 在生长锥的半个区域的局部失活导致生长锥远离照射部位。相反，CRMP2 的局部失活导致生长锥转向照射部位。这些发现表明 CRMP1 和 CRMP2 在生长锥行为和神经突生长中具有不同的功能。 (C) 2012 Wiley periodicals, Inc. 开发 Neurobiol，2012
Collapsin response mediator protein 1 (CRMP1) and CRMP2 have been known as mediators of extracellular guidance cues such as semaphorin 3A and contribute to cytoskeletal reorganization in the axonal pathfinding process. To date, how CRMP1 and CRMP2 focally regulate axonal pathfinding in the growth cone has not been elucidated. To delineate the local functions of these CRMPs, we carried out microscale-chromophore-assisted light inactivation (micro-CALI), which enables investigation of localized molecular functions with highly spatial and temporal resolutions. Inactivation of either CRMP1 or CRMP2 in the neurite shaft led to arrested neurite outgrowth. Micro-CALI of CRMP2 in the central domain of the growth cones consistently arrested neurite outgrowth, whereas micro-CALI of CRMP1 in the same region caused significant lamellipodial retraction, followed by retardation of neurite outgrowth. Focal inactivation of CRMP1 in its half region of the growth cone resulted in the growth cone turning away from the irradiated site. Conversely, focal inactivation of CRMP2 resulted in the growth cone turning toward the irradiated site. These findings suggest different functions for CRMP1 and CRMP2 in growth cone behavior and neurite outgrowth. (C) 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2012