Collapsin Response Mediator Proteins: Their Biological Functions and Pathophysiology in Neuronal Development and Regeneration.

Fumio Nakamura,Yoshio Goshima,Toshio Ohshima

doi:10.3389/fncel.2020.00188

Abstract

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.

Highlights

Cell to cell interactions mediated by extracellular molecules drives numerous physiological processes and helps enable coordinated functioning in neuronal development and regeneration
We summarize the molecular aspects of the Collapsin response mediator proteins (CRMPs) and discuss their possible involvement in pathophysiological conditions of various disease states
As Rho-kinase acts as the downstream molecule of lysophosphatidic acid (LPA), the primary cultured dorsal root ganglion (DRG) neurons stimulated with LPA induced CRMP2-Thr555 phosphorylation (Figure 2)

Summary

Introduction

Cell to cell interactions mediated by extracellular molecules drives numerous physiological processes and helps enable coordinated functioning in neuronal development and regeneration. The N-terminal extended region has several unique functions such as distal localization of L-CRMP2 (CRMP2A) in axons (Balastik et al, 2015), L-CRMP4 (CRMP4b) and RhoA interaction in Nogo signaling (Alabed et al, 2007), and correlation of L-CRMP1 expression and cancer cell migration (Pan et al, 2011). Using the phosphorylation-mimicking form of CRMP2, Sumi et al (2018) revealed that the increased negative charge of the C-terminal region alters CRMP2 homo-tetramer conformation and reduces the interaction of CRMP2 and tubulin-dimers.

Results

Conclusion