Nakamura Fumio, Ohshima Toshio, Goshima Yoshio
Department of Biochemistry, Tokyo Women's Medical University, Tokyo, Japan.
Department of Life Science and Medical Bio-Science, Waseda University, Tokyo, Japan.
Front Cell Neurosci. 2020 Jun 23;14:188. doi: 10.3389/fncel.2020.00188. eCollection 2020.
Collapsin response mediator proteins (CRMPs), which consist of five homologous cytosolic proteins, are one of the major phosphoproteins in the developing nervous system. The prominent feature of the CRMP family proteins is a new class of microtubule-associated proteins that play important roles in the whole process of developing the nervous system, such as axon guidance, synapse maturation, cell migration, and even in adult brain function. The CRMP C-terminal region is subjected to posttranslational modifications such as phosphorylation, which, in turn, regulates the interaction between the CRMPs and various kinds of proteins including receptors, ion channels, cytoskeletal proteins, and motor proteins. The gene-knockout of the CRMP family proteins produces different phenotypes, thereby showing distinct roles of all CRMP family proteins. Also, the phenotypic analysis of a non-phosphorylated form of CRMP2-knockin mouse model, and studies of pharmacological responses to CRMP-related drugs suggest that the phosphorylation/dephosphorylation process plays a pivotal role in pathophysiology in neuronal development, regeneration, and neurodegenerative disorders, thus showing CRMPs as promising target molecules for therapeutic intervention.
塌陷反应介导蛋白（CRMPs）由五种同源胞质蛋白组成，是发育中的神经系统中的主要磷蛋白之一。CRMP家族蛋白的突出特点是一类新型的微管相关蛋白，在神经系统发育的整个过程中发挥重要作用，如轴突导向、突触成熟、细胞迁移，甚至在成人大脑功能中也发挥作用。CRMP的C末端区域会发生磷酸化等翻译后修饰，这反过来又调节CRMP与包括受体、离子通道、细胞骨架蛋白和运动蛋白在内的各种蛋白质之间的相互作用。CRMP家族蛋白的基因敲除产生不同的表型，从而显示出所有CRMP家族蛋白的不同作用。此外，对CRMP2基因敲入小鼠模型的非磷酸化形式的表型分析以及对CRMP相关药物的药理反应研究表明，磷酸化/去磷酸化过程在神经元发育、再生和神经退行性疾病的病理生理学中起关键作用，因此表明CRMPs是有前景的治疗干预靶分子。
