8.A.228.  The Collapsin Response Mediator Protein 2 (CRMP2) Family

It plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration (Inagaki et al. 2001; Cole et al. 2004). It is necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton, and it  may play a role in endocytosis. CRMP2 blocked NaV1.7 (TC# 1.A.1.10.5) function and was antinociceptive in rodent models of neuropathic pain. A CRMP2 regulatory sequence (CRS), unique to NaV1.7, is essential for regulatory coupling. CRMP2 preferentially bound to the NaV1.7 CRS over other NaV isoforms. Substitution of the NaV1.7 CRS with the homologous domains from the other eight VGSC isoforms decreased NaV1.7 currents. A cell-penetrant decoy peptide corresponding to the NaV1.7-CRS reduced NaV1.7 currents and trafficking, decreased presynaptic NaV1.7 expression, reduced spinal CGRP release, and reversed nerve injury-induced mechanical allodynia (Gomez et al. 2023).

 


 


 

References:

Cole, A.R., A. Knebel, N.A. Morrice, L.A. Robertson, A.J. Irving, C.N. Connolly, and C. Sutherland. (2004). GSK-3 phosphorylation of the Alzheimer epitope within collapsin response mediator proteins regulates axon elongation in primary neurons. J. Biol. Chem. 279: 50176-50180.
Gomez, K., H.J. Stratton, P. Duran, S. Loya, C. Tang, A. Calderon-Rivera, L. François-Moutal, M. Khanna, C.L. Madura, S. Luo, B. McKiver, E. Choi, D. Ran, L. Boinon, S. Perez-Miller, M.I. Damaj, A. Moutal, and R. Khanna. (2023). Identification and targeting of a unique Na1.7 domain driving chronic pain. Proc. Natl. Acad. Sci. USA 120: e2217800120.
Inagaki, N., K. Chihara, N. Arimura, C. Ménager, Y. Kawano, N. Matsuo, T. Nishimura, M. Amano, and K. Kaibuchi. (2001). CRMP-2 induces axons in cultured hippocampal neurons. Nat Neurosci 4: 781-782.
Examples:

TC#NameOrganismal TypeExample
8.A.228.1.1

CRMP2 (DPYSL2) of 572 aas.  It regulates the activity of Na2+ channel, Nav1.7 preferentially (Gomez et al. 2023), thereby eliminating chronic neuropathic pain. See family description for details.

CRMP2 of Homo sapiens

 
8.A.228.1.2

Dihydropyrimidinase (phenylhydantoinase), HydA, of 475 aas.

HydA of Paenibacillus odorifer