Cdc2-mediated Schwann cell migration during peripheral nerve regeneration.
Schwann cell migration facilitates peripheral nerve regeneration after injury. We have recently found increased activation of Cdc2 kinase in regenerating sciatic nerves. Here we show that Cdc2 phosphorylation of caldesmon regulates Schwann cell migration and nerve regeneration. A robust but transient increase in Cdc2 expression was found in cultured Schwann cells prepared from the sciatic nerve in rats that had undergone crush injury for 7 days. These ;injury-preconditioned' Schwann cells exhibited enhanced migration compared with non-preconditioned control cells and treatment with the cdk inhibitor roscovitine prevented cell migration. After transduction with recombinant Cdc2 DNA adenoviral vectors, Schwann cells were implanted into sciatic nerves; those expressing wild-type Cdc2 migrated further in the distal direction than those expressing dominant-negative Cdc2. We identified caldesmon as a downstream substrate of Cdc2 in Schwann cells and its phosphorylation by Cdc2 changed its subcellular localization. Overexpression of dominant-negative caldesmon significantly counteracted the migration effect caused by Cdc2. Finally, neurite outgrowth of cultured DRG sensory neurons, facilitated by co-culture with injury-preconditioned Schwann cells, was suppressed by roscovitine treatment. The results indicate that activation of the Cdc2-caldesmon pathway is necessary for Schwann cell migration and suggest a role for this pathway in peripheral axonal growth.
Han
In Sun
IS
Department of Oriental Medicine, Daejeon University, Daejeon 300-716, Korea.
Seo
Tae Beom
TB
Kim
Kwan-Hoi
KH
Yoon
Jin-Hwan
JH
Yoon
Sung-Jin
SJ
Namgung
Uk
U
D000818:Animals; D016203:CDC2 Protein Kinase / Q000096:biosynthesis / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004790:Enzyme Induction; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D008297:Male; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D009475:Neurons, Afferent / Q000378:metabolism; D009924:Organ Culture Techniques; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000254:growth & development; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D014357:Trypsin / Q000494:pharmacology
D012333:RNA, Messenger; D016203:CDC2 Protein Kinase; D014357:Trypsin