Molecular characterization of CRMP5, a novel member of the collapsin response mediator protein family

The CRMP (collapsin response mediator protein) family is thought to play ke y roles in growth cone guidance during neural development. The four members (CRMP1-4) identified to date have been demonstrated to form hetero-multime ric structures through mutual associations. In this study, we cloned a nove l member of this family, which we call CRMP5, by the yeast two-hybrid metho d. This protein shares relatively low amino acid identity with the other CR MP members (49-50%) and also with dihydropyrimidinase (51%), whereas CRMP1- 4 exhibit higher identity with each other (68-75%), suggesting that CRMP5 m ight be categorized into a third subfamily. The mouse CRMP5 gene was locate d at chromosome 5 B1, Northern blot and in situ hybridization analyses indi cated that CRMP5 is expressed throughout the nervous system similarly to th e other members (especially CRMP1 and CRMP4) with the expression peak in th e first postnatal week. Association experiments using the yeast two-hybrid method and coimmunoprecipitation showed that CRMP5 interacts with dihydropy rimidinase and all the CRMPs including itself, except for CRMP1, although t he expression profile almost overlaps with that of CRMP1 during development . These results suggest that CRMP complexes in the developing nervous syste m are classifiable into two populations that contain either CRMP1 or CRMP5. This indicates that different complexes may have distinct functions in sha ping the neural networks.