Nedd9 protein, a Cas-L homologue, is upregulated after transient global ischemia in rats: Possible involvement of Nedd9 in the differentiation of neurons after ischemia

Takahiro Sasaki, Satoshi Iwata, Hirotaka James Okano, Yasuyo Urasaki, Junichi Hamada, Hirotoshi Tanaka, Nam H. Dang, Hideyuki Okano, Chikao Morimoto

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Background and Purpose - Some proteins involved in self-repair after stroke in the adult brain are primarily expressed during embryonic development and strongly down-regulated during the early postnatal phase. Neuronal precursor cell-expressed, developmentally down-regulated gene (Nedd) 9 was recognized to be identical to Crk-associated substrate lymphocyte type (Cas-L), a docking protein that associates with a variety of signaling molecules, such as focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (Pyk2), and Crk. We investigated the involvement of these proteins in the pathophysiology of global cerebral ischemia. Methods - The mouse Cas-L/Nedd9 cDNAs were cloned. The expression and function of Cas-L/Nedd9 protein in the pathogenesis of global ischemia in rats was investigated by RT-PCR, Western blot analysis, and immunohistochemistry. The neurite outgrowth of the transfectants of Nedd9 deletion mutants in PC-12 cells was also assessed to clarify the function of the Nedd9 protein. Results - Nedd9 was a splicing variant of Cas-L and was selectively induced in neurons of the cerebral cortex and hippocampus 1 to 14 days after the ischemia. Induced Nedd9 protein was tyrosine phosphorylated and was bound to FAK in dendrite and soma of neurons after the ischemia. Finally, it was demonstrated that Nedd9 promoted neurite outgrowth of PC-12 cells. Conclusions - Our study may support the potential of Nedd9 for participation in the differentiation of neurons after global ischemia in rats.

Original languageEnglish
Pages (from-to)2457-2462
Number of pages6
JournalStroke
Volume36
Issue number11
DOIs
Publication statusPublished - 2005 Nov

Keywords

  • Cerebral ischemia
  • Global
  • Neural differentiation
  • Rats

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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