MOLECULAR-CLONING OF A NEW UNC-33-LIKE CDNA FROM RAT-BRAIN AND ITS RELATION TO PARANEOPLASTIC NEUROLOGICAL SYNDROMES

Anti-CV2-autoantibodies from patients with paraneoplastic neurological syndromes were used to purify protein(s) related to this disease. A n ovel cDNA, c-22, was obtained by PCR with primers based on amino-acid sequence of peptides obtained from this protein and rat brain cDNA as template. The deduced amino-acid sequence of c-22 shows homology to th e Unc-33 gene from C. elegans in which mutations lead to defects in ne uritic outgrowth and axonal guidance and cause uncoordinated movements of the nematode. Several consensus sites for putative protein kinase C phosphorylation were found, suggesting that the c-22 gene product ma y be a phosphoprotein. Northern hybridizations show that the apparentl y unique 3.8-kb mRNA of c-22 is present in rat brain tissue and its ex pression is developmentally regulated: the levels of C-22 mRNA, detect able in brain at embryonic day 17 (E17), increase up to post-natal day 7 (P7) and decline rapidly to an almost undetectable level in adult.