P311 accelerates nerve regeneration of the axotomized facial nerve.
In axotomized adult neurons, a process of axonal regrowth and re-establishment of the neuronal function has to be activated. Developmentally regulated factors may be reactivated during neuronal regeneration. Here we identify a gene, previously designated P311, that is up-regulated in the axotomized facial motoneurons. Ectopically expressed P311 localizes in the cytoplasm and the nucleus. Over-expression of P311 induces p21(WAF1/Cip1) expression, leading PC12 cells to differentiate and to have neuron-like morphologies. Adenovirus-mediated P311 gene transfer promotes neurite outgrowth of postnatal dorsal root ganglion neurons and embryonic hippocampal neurons in vitro. This effect is abolished by the activation of Rho kinase. P311 also facilitates nerve regeneration following facial nerve injury in vivo. Our data provide evidence that genes involved in the differentiation process contribute to the regeneration of injured mature neurons, and may provide a practical molecular target.
Fujitani
Masashi
M
Department of Neurobiology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Yamagishi
Satoru
S
Che
Yong Ho
YH
Hata
Katsuhiko
K
Kubo
Tateki
T
Ino
Hidetoshi
H
Tohyama
Masaya
M
Yamashita
Toshihide
T
D000818:Animals; D019771:Axotomy; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005154:Facial Nerve / Q000378:metabolism / Q000502:physiology*; D020220:Facial Nerve Injuries / Q000188:drug therapy* / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D023421:Models, Animal; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016501:Neurites / Q000502:physiology; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000502:physiology; D054460:rho-Associated Kinases
C493958:Cdkn1a protein, rat; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047908:Intracellular Signaling Peptides and Proteins; C428027:NREP protein, human; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases