BM180 - A NOVEL BASEMENT-MEMBRANE PROTEIN WITH A ROLE IN STIMULUS-SECRETION COUPLING BY LACRIMAL ACINAR-CELLS

Regulated secretion requires the developmental coupling of neuronal or hormonal stimuli to an exocytotic response, a multistep pathway whose appearance may be linked with cellular adhesion to the newly formed e xocrine cell basement membrane. We screened for adhesion-associated co upling activity using lacrimal acinar cells and have identified ''BM18 0,'' a novel basement membrane protein enriched in guanidine HCl extra cts of lacrimal and parotid exocrine secretory glands. BM180 resides p rimarily in a previously unexamined lower molecular-mass basement memb rane peak (peak 2) that contains cell adhesion activity inhibitable wi th the anti-BM180 monoclonal antibody 3E12. Removal of peak 2 by gel f iltration or preincubation of basement membrane with 3E12 decreased re gulated peroxidase secretion by one-half without affecting constitutiv e secretion or the amount of cellular peroxidase available for release . Adding back peak 2 restored regulated secretion in a dose-dependent and 3E12-inhibitable maimer and suggested a synergistic relationship b etween BM180 and laminin 1. BM180 has a mobility of 180 and 60 kDa in the absence or presence of dithiothreitol, respectively, and shows no immunological identity by competitive enzyme-linked immunosorbent assa y with laminin 1, collagen TV, entactin, fibronectin, BM-40, perlecan, or vitronectin. We propose that BM180 is an important resident of cer tain glandular basement membranes where it interacts with the cell sur face, thereby possibly signaling the appearance of a transducing eleme nt in the stimulus-secretion coupling pathway.