title: Collapsin response mediator protein-2 is a calmodulin-binding protein.
abstract: Collapsin response mediator protein-2 (CRMP-2) plays a crucial role in axonal guidance and neurite outgrowth during neural development and regeneration. We have studied the interaction between calmodulin (CaM) and CRMP-2 and how Ca(2+)/CaM binding modulates the biological functions of CRMP-2. We have shown that CRMP-2 binds to CaM directly in a Ca(2+)-dependent manner. The CaM binding site of CRMP-2 is proposed to reside in the last helix of the folded domain, and in line with this, a synthesized peptide representing this helix bound to CaM. In addition, CaM binding inhibits a homotetrameric assembly of CRMP-2 and attenuates calpainmediated CRMP-2 proteolysis. Furthermore, a CaM antagonist reduces the number and length of process induced by CRMP-2 overexpression in HEK293 cells. Take together, our data suggest that CRMP-2 is a novel CaM-binding protein and that CaM binding may play an important role in regulating CRMP-2 functions.
authors.affiliation: Center of Innovative Research, Banyan Biomarkers Inc, 12805 Research Drive, Alachua, FL 32615, USA. zqzhang@banyanbio.com
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: V
authors.initials: V
authors.lastname: Majava
authors.forename: A
authors.initials: A
authors.lastname: Greffier
authors.forename: R L
authors.initials: RL
authors.lastname: Hayes
authors.forename: P
authors.initials: P
authors.lastname: Kursula
authors.forename: K K W
authors.initials: KK
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; C095114:collapsin response mediator protein-2; D002154:Calpain; D002118:Calcium