Calreticulin-integrin bidirectional signaling complex

Calreticulin has multiple functions, diverse cellular locations, and putative isoforms. It likely maintains integrin avidity by binding alpha integrin cytoplasmic tails and is a surface lectin which triggers cell spreading. In the present study, we have immunocaptured a cell surface complex from B16 mouse melanoma cells which contains alpha(6)B(1) integrin, two molecular forms of calreticulin, and KDEL docking protein (KDEL-R). One of the calreticulins, ''endocalreticulin'', a 52 kDa protein, does not become surface biotinylated, and is probably bound to alpha integrin cytoplasmic tails; it disappears when B16 cells adhere to laminin, and two ubiquitinated calreticulins appear. One ubiquitinated species, a 125 kDa protein, is restricted to focal contacts whereas a second species, a 75 kDa protein, is in focal contacts and surrounding plasma membrane; it also arises when cells bind non-specific surfaces. The other calreticulin, ''ectocalreticulin'', a 62 kDa protein, becomes surface biotinylated, is probably anchored to surface KDEL-R, and cooperates with alpha(6) beta(1) integrin, triggering cell spreading. The present results suggest a model in which calreticulin-integrin surface complex functions as a symbiotic unit, transmitting information in both directions across the plasma membrane. (C) 1997 Academic Press.