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First published online 2 January 2007
doi: 10.1242/jcs.03322

Journal of Cell Science 120, 246-255 (2007)
Published by The Company of Biologists 2007
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Research Article

Cdc2-mediated Schwann cell migration during peripheral nerve regeneration

In Sun Han1,*, Tae Beom Seo1,*, Kwan-Hoi Kim2, Jin-Hwan Yoon3, Sung-Jin Yoon4 and Uk Namgung1,{ddagger}

1 Department of Oriental Medicine, Daejeon University, Daejeon 300-716, Korea,
2 Department of Pharmacology, School of Medicine, Pusan National University, Busan, Korea
3 Department of Sports and Leisure Studies, Hannam University, Daejeon 300-791, Korea
4 Department of Physical Education, Korea University, Seoul, Korea

{ddagger} Author for correspondence (e-mail: unamgung{at}dju.ac.kr)

Accepted 30 October 2006

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.

Key words: Migration, Schwann cells, Cdc2, Caldesmon, Axonal regeneration, Sciatic nerve


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JCS 2007 120: 203. [Full Text]  





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