期刊
CELLULAR SIGNALLING
卷 21, 期 12, 页码 1818-1826出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2009.07.017
关键词
CRMP-2; Tubulin; GTPase activity; Regulation; Microtubule
类别
资金
- Ministry of Education, Science and Technology in the Republic of Korea [FPR08B1-160/300]
- National Research Foundation of Korea [13-2008-00-047-00] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Collapsin response mediator protein-2 (CRMP-2) plays a key role in axonal development by regulating microtubule dynamics. However, the molecular mechanisms underlying this function have not been clearly elucidated. In this study, we demonstrated that hCRMP-2, specifically amino acid residues 480-509, is essential for stimulating tubulin GTPase activity. We also found that the GTPase-activating protein (GAP) activity of hCRMP-2 was important for microtubule assembly and neurite formation in differentiated PC12 pheochromocytoma cell lines. Mutant hCRMP-2, lacking arginine residues responsible for GAP activity, inhibited microtubule assembly and neurite formation. Interestingly, we found that the N-terminal region (amino acids 150-299) of hCRMP-2 had an inhibitory role on GAP activity via a direct interaction with the C-terminal region (amino acids 480-509). Our results suggest that CRMP-2 as a tubulin direct binder may be a GAP of tubulin in neurite formation and that its CAP activity may be regulated by an intramolecular interaction with an N-terminal inhibitory region. (C) 2009 Elsevier Inc. All rights reserved.
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