Collapsin response mediator protein-2 regulates neurite formation by modulating tubulin GTPase activity
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- Collapsin response mediator protein-2 regulates neurite formation by modulating tubulin GTPase activity
- Chae, Young Chan; Lee, Sukmook; Heo, Kyun; Ha, Sang Hoon; Jung, Yonwoo; Kim, Jong Hyun; Ihara, Yasuo; Suh, Pann-Ghill; Ryu, Sung Ho
- Issue Date
- ELSEVIER SCIENCE INC
- CELLULAR SIGNALLING, v.21, no.12, pp.1818 - 1826
- 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.
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