Collapsin response mediator protein-2 regulates neurite formation by modulating tubulin GTPase activity.
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.
Chae
Young Chan
YC
Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, 790-784, Republic of Korea.
Lee
Sukmook
S
Heo
Kyun
K
Ha
Sang Hoon
SH
Jung
Yonwoo
Y
Kim
Jong Hyun
JH
Ihara
Yasuo
Y
Suh
Pann-Ghill
PG
Ryu
Sung Ho
SH
D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000166:cytology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000648:ultrastructure; D009154:Mutation; D020932:Nerve Growth Factor / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D014404:Tubulin / Q000032:analysis / Q000378:metabolism*; D014709:Vero Cells
D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D014404:Tubulin; C095114:collapsin response mediator protein-2; D020932:Nerve Growth Factor