Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Japan.
Dev Neurobiol. 2012 Dec;72(12):1528-40. doi: 10.1002/dneu.22017. Epub 2012 Aug 23.
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.
collapsin 反应介质蛋白 1 (CRMP1) 和 CRMP2 已被认为是细胞外导向线索（如神经 3A 素）的介质，有助于轴突寻路过程中的细胞骨架重组。迄今为止，CRMP1 和 CRMP2 如何在生长锥中局部调节轴突寻路尚未阐明。为了描绘这些 CRMP 的局部功能，我们进行了微尺度发色团辅助光失活 (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。在神经突干中失活 CRMP1 或 CRMP2 都会导致神经突生长停止。CRMP2 在生长锥中央域的 micro-CALI 一致地导致神经突生长停止，而 CRMP1 在同一区域的 micro-CALI 导致明显的片状伪足回缩，随后生长锥的神经突生长减慢。CRMP1 在生长锥的一半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。
