IDENTIFICATION AND CHARACTERIZATION OF THE HUMAN CELL-ADHESION MOLECULE CONTACTIN

We have prepared a monoclonal antibody, Neuro-1, that recognizes the h uman homolog of the chicken contactin/F11 and mouse F3 cell adhesion m olecules. The Neuro-1 antigen, structurally characterized as a 135 kDa glycosylphosphatidylinositol-linked glycoprotein, was immunoaffinity purified and partially sequenced. Comparison of an internal peptide se quence to that predicted from the chicken contactin/F11, mouse F3 and human contactin (reported herein) cDNA sequence identifies the Neuro-1 antigen as human contactin. Moreover, a polyclonal antisera generated against the purified Neuro-1 antigen was immunoreactive with a fragme nt of human contactin expressed in bacteria. The complete coding and d educed amino acid sequences of human contactin were determined and are 86% and 95% identical to the respective mouse F3 sequences. Structura l features shared with contactin/F11/F3 include six immunoglobulin typ e C2 and four fibronectin type III-like domains, multiple sites for as n-linked glycosylation and a COOH-terminal signal peptide presumably r emoved during the generation of a phosphatidylinositol cell surface li nkage. The potential for glycosylation and GPI-linkage is also consist ent with protein chemical studies of human contactin. Contactin mRNA e xpression was characterized using Northern blot analyses of human tiss ues and cell lines. High level expression of a single contactin transc ript in adult brain, and low level expression of multiple transcripts in lung, pancreas, kidney and skeletal muscle are observed. Highly exp ressed multiple transcripts, similar in pattern to that of pancreas, l ung, kidney and skeletal muscle, are also observed in human neuroblast oma and retinoblastoma cell lines.