RT Journal Article
SR Electronic
T1 Collapsin Response Mediator Protein 4 (CRMP4) Facilitates Wallerian Degeneration and Axon Regeneration following Sciatic Nerve Injury
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0479-19.2020
DO 10.1523/ENEURO.0479-19.2020
VO 7
IS 2
A1 Marie-Pier Girouard
A1 Tristan Simas
A1 Luyang Hua
A1 Barbara Morquette
A1 Mohamad R. Khazaei
A1 Nicolas Unsain
A1 Aaron D. Johnstone
A1 Isabel Rambaldi
A1 Ricardo L. Sanz
A1 Marie-Eve Di Raddo
A1 Kanchana K. Gamage
A1 Yu Yong
A1 Dianna E. Willis
A1 Valerie M. K. Verge
A1 Philip A. Barker
A1 Christopher Deppmann
A1 Alyson E. Fournier
YR 2020
UL http://www.eneuro.org/content/7/2/ENEURO.0479-19.2020.abstract
AB In contrast to neurons in the CNS, damaged neurons from the peripheral nervous system (PNS) regenerate, but this process can be slow and imperfect. Successful regeneration is orchestrated by cytoskeletal reorganization at the tip of the proximal axon segment and cytoskeletal disassembly of the distal segment. Collapsin response mediator protein 4 (CRMP4) is a cytosolic phospho-protein that regulates the actin and microtubule cytoskeleton. During development, CRMP4 promotes growth cone formation and dendrite development. Paradoxically, in the adult CNS, CRMP4 impedes axon regeneration. Here, we investigated the involvement of CRMP4 in peripheral nerve injury in male and female Crmp4−/− mice following sciatic nerve injury. We find that sensory axon regeneration and Wallerian degeneration are impaired in Crmp4−/− mice following sciatic nerve injury. In vitro analysis of dissociated dorsal root ganglion (DRG) neurons from Crmp4−/− mice revealed that CRMP4 functions in the proximal axon segment to promote the regrowth of severed DRG neurons and in the distal axon segment where it facilitates Wallerian degeneration through calpain-dependent formation of harmful CRMP4 fragments. These findings reveal an interesting dual role for CRMP4 in proximal and distal axon segments of injured sensory neurons that coordinately facilitate PNS axon regeneration.