Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10816860 | Cellular Signalling | 2009 | 9 Pages |
Abstract
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 acids150-299) 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 GAP activity may be regulated by an intramolecular interaction with an N-terminal inhibitory region.
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Authors
Young Chan Chae, Sukmook Lee, Kyun Heo, Sang Hoon Ha, Yonwoo Jung, Jong Hyun Kim, Yasuo Ihara, Pann-Ghill Suh, Sung Ho Ryu,