LAMININ-BINDING PROTEIN-120 FROM BRAIN IS CLOSELY-RELATED TO THE DYSTROPHIN-ASSOCIATED GLYCOPROTEIN, DYSTROGLYCAN, AND BINDS WITH HIGH-AFFINITY TO THE MAJOR HEPARIN-BINDING DOMAIN OF LAMININ

When brain proteins separated by SDS-polyacrylamide gel electrophoresi s (PAGE) and transferred to nitrocellulose are probed with I-125-label ed laminin, a single broad band of approximately 120 kDa binds laminin specifically. We show here by two-dimensional electrophoresis and pro tein microsequencing that this band consists of two distinct laminin-b inding proteins. One of these is the amyloid precursor protein. The ot her, laminin-binding protein (LBP) 120, is closely related to the dyst rophin-associated glycoprotein, dystroglycan (156 kDa); 5 peptides fro m purified bovine brain LBP120, ranging in size from 7 to 19 residues, are up to 100% identical to the predicted amino acid sequence of musc le dystroglycan (Ibraghimov-Beskrovnaya, O., Ervasti, J. M., Leveille, C. J., Slaughter, C. A., Sernett, S. W., and Campbell, K. P. (1992) N ature 355, 696-702). These protein microsequence data support the data of Ibraghimov-Beskrovnaya et al., which suggest that the dystroglycan precursor is processed into 120/156- and 43-kDa proteins. Moreover, t he data suggest a revision in the position of the proposed cleavage si te of the precursor. The glycosylation and extracellular localization of LBP120/dystroglycan are consistent with it being a cell surface lam inin receptor. LBP120/dystroglycan, either as a native protein, or fol lowing SDS-PAGE and transfer to nitrocellulose, binds with high affini ty (K(d) = 90 nM) to a proteolytic fragment of laminin (E3) containing the major heparin binding domain. This binding is Ca2+-dependent and inhibited by low concentrations of heparin. Thus, LBP120/dystroglycan is a major non-integrin laminin receptor whose high affinity interacti on with laminin may reflect a structural role in brain and muscle.