Genetic inhibition of CRMP2 phosphorylation at serine 522 promotes axonal regeneration after optic nerve injury

Shunsuke Kondo, Kazuya Takahashi, Yuki Kinoshita, Jun Nagai, Shuji Wakatsuki, Toshiyuki Araki, Yoshio Goshima, Toshio Ohshima

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Abstract

Axonal degeneration occurs in various neurological diseases and traumatic nerve injury, and axonal regeneration is restricted by inhibitory factors in the central nervous system. Cyclin-dependent kinase 5 and glycogen synthase kinase 3β (GSK3β) are activated by one of those inhibitors, and collapsin response mediator protein 2 (CRMP2) is phosphorylated by both kinases. We previously developed a CRMP2 knock-in (CRMP2 KI) mouse line, in which CRMP2 phosphorylation at Ser 522 is inhibited. Because CRMP2 KI mice showed promotion of axonal regeneration after spinal cord injury, we hypothesized that CRMP2 KI mice would show higher axonal regeneration after optic nerve injury. In this study, we first show that depolymerization of microtubules after optic nerve crush (ONC) injury was suppressed in CRMP2 KI mice. Loss of retinal ganglia cells was also reduced after ONC. We found that protein level of GAP43, a marker of regenerative axons, was higher in the optic nerve from CRMP2KI than that from wild type 4 weeks after of ONC. We further observed increased numbers of axons labeled by tracer in the optic nerve after ONC in CRMP2 KI mice. These results suggest that inhibition of phosphorylation of CRMP2 suppresses axonal degeneration and promotes axonal regeneration after optic nerve injury.

Original languageEnglish
Article number7188
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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Optic Nerve Injuries
Serine
Regeneration
Phosphorylation
Nerve Crush
Optic Nerve
Axons
Cyclin-Dependent Kinase 5
GAP-43 Protein
Glycogen Synthase Kinase 3
collapsin response mediator protein-2
Retinal Ganglion Cells
Spinal Cord Injuries
Microtubules
Phosphotransferases
Central Nervous System

ASJC Scopus subject areas

  • General

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Genetic inhibition of CRMP2 phosphorylation at serine 522 promotes axonal regeneration after optic nerve injury. / Kondo, Shunsuke; Takahashi, Kazuya; Kinoshita, Yuki; Nagai, Jun; Wakatsuki, Shuji; Araki, Toshiyuki; Goshima, Yoshio; Ohshima, Toshio.

In: Scientific reports, Vol. 9, No. 1, 7188, 01.12.2019.

Research output: Contribution to journalArticle

Kondo, Shunsuke ; Takahashi, Kazuya ; Kinoshita, Yuki ; Nagai, Jun ; Wakatsuki, Shuji ; Araki, Toshiyuki ; Goshima, Yoshio ; Ohshima, Toshio. / Genetic inhibition of CRMP2 phosphorylation at serine 522 promotes axonal regeneration after optic nerve injury. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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