Collapsin response mediator protein-2 accelerates axon regeneration of nerve-injured motor neurons of rat.
The rat collapsin response mediator protein-2 (CRMP-2) is a member of CRMP family (CRMP-1-5). The functional consequence of CRMP-2 during embryonic development, particularly in neurite elongation, is relatively understood; however, the role in nerve regeneration is unclear. Here we examined the role of CRMP-2 during nerve regeneration using rat hypoglossal nerve injury model. Among the members, CRMP-1, CRMP-2, CRMP-5 mRNA expressions increased after nerve injury, whereas CRMP-3 and CRMP-4 mRNA did not show any significant change. In the N1E-115 cells, CRMP-2 has the most potent neurite elongation activity among the CRMP family members. In dorsal root ganglion (DRG) organ culture, CRMP-2 overexpression by adenoviral vector demonstrated substantial neurite elongation. On the other hand, CRMP-2 (DeltaC381), which acts as a dominant negative form of CRMP-2, inhibited neurite formation. Collectively, it would be plausible that CRMP-2 has potent nerve regeneration activity after nerve injury. We therefore examined whether CRMP-2 overexpression in the injured hypoglossal motor neurons accelerates nerve regeneration. A retrograde-tracer, Fluoro-Gold (FG), was used to evaluate the number of reprojecting motor neurons after nerve injury. CRMP-2-overexpressing motor neurons demonstrated the accelerated reprojection. The present study suggests that CRMP-2 has potent neurite elongation activity in nerve regeneration in vivo.
Suzuki
Yasuhiro
Y
Department of Anatomy & Neurobiology, Osaka City University, Graduate School of Medicine, Osaka, Japan.
Nakagomi
Saya
S
Namikawa
Kazuhiko
K
Kiryu-Seo
Sumiko
S
Inagaki
Naoyuki
N
Kaibuchi
Kozo
K
Aizawa
Hitoshi
H
Kikuchi
Kenjiro
K
Kiyama
Hiroshi
H
D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology; D007002:Hypoglossal Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000098855:Collapsin Response Mediator Protein 1
D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D000098855:Collapsin Response Mediator Protein 1; C095114:collapsin response mediator protein-2