UTROPHIN-DYSTROGLYCAN COMPLEX IN MEMBRANES OF ADHERENT CULTURED-CELLS

In skeletal muscle, dystrophin binds to an oligomeric, transmembrane c omplex (DAGc; dystrophin-associated glycoprotein complex) which intera cts with laminin in the extracellular matrix. We now present biochemic al evidence for an association between utrophin (dystrophin-related pr otein, DRP) and a major DAGc component, beta-dystroglycan (43DAG) in c ultured cell lines which contain little if any dystrophin. We have sho wn also that utrophin and beta-dystroglycan co-localise at or near the plasma membrane and that they co-sediment in large complexes on sucro se density gradients. On the lower plasma membrane, in contact with th e substratum, part of the utrophin and beta-dystroglycan staining co-l ocalised with alpha-actinin in a punctate distribution outside classic al vinculin-rich focal adhesions. beta-dystroglycan, utrophin, syntrop hin (59DAP), and alpha-actinin were found in all adhesion-competent ce ll lines studied, but levels of the last three proteins were greatly r educed in myeloma cells, which cannot readily attach to substrata. Pos sible roles for utrophin in cultured cells are considered in the light of recent evidence for involvement of utrophin-glycoprotein complexes in muscle in signal transduction and recruitment of acetylcholine rec eptors to neuromuscular junctions. (C) 1996 Wiley-Liss, Inc.