R. Inatome et al., Identification of CRAM, a novel unc-33 gene family protein that associateswith CRIMP3 and protein-tyrosine kinase(s) in the developing rat brain, J BIOL CHEM, 275(35), 2000, pp. 27291-27302
Four members of collapsin response mediator proteins (CRMPs) are thought to
be involved in the semaphorin-induced growth cone collapse during neural d
evelopment. Here we report the identification of a novel CRMPS associated p
rotein, designated CRAM for CRMP3-associated molecule, that belongs to the
unc-33 gene family. The deduced amino acid sequence reveals that the CRAM g
ene encodes a protein of 563 amino acids, shows 57% identity with dihydropy
rimidinase, and shows 50-51% identity with CRMPs. CRAM appears to form a la
rge complex composed of CRMPS and other unidentified proteins in vivo. Inde
ed, CRAM physically associates with CRMPS when co-expressed in COS-7 cells.
The expression of CRAM is brain-specific, is high in fetal and neonatal ra
t brain, and decreases to very low levels in adult brain. Moreover, CRAM ex
pression is up-regulated during neuronal differentiation of embryonal carci
noma P19 and PC12 cells. Finally, immunoprecipitation analysis of rat brain
extracts shows that CRAM is co-immunoprecipitated with proteins that conta
in protein-tyrosine kinase activity, Taken together, our results suggest th
at CRAM, which interacts with CRMP3 and protein-tyrosine kinase(s), is a ne
w member of an emerging family of molecules that potentially mediate signal
s involved in the guidance and outgrowth of axons.