Roles of molecular chaperones in pancreatic secretion and their involvement in intestinal absorption

This review focuses on the contribution of molecular chaperones in the secr etory process of digestive enzymes and their interaction with enterocytes. By using biochemistry and immunocytochemistry, we have shown that Grp94, Cp n10, Cpn60, and protein disulfide isomerase (PDI) are present all along the rough endoplasmic reticulum-Golgi-granule secretory pathway of the pancrea tic acinar cells and are secreted into the acinar lumen. Two other molecula r chaperones, Grp78 and the Hsp70, appear to be restricted to the rough end oplasmic reticulum and the trans-Golgi apparatus, respectively We have foun d that chaperones can be associated with pancreatic enzymes along the secre tory pathway. Indeed, double immunogold and immunocoprecipitation revealed an association between Cpn60 and the colipase-dependent lipase (CDL) and be tween Grp94 and the bile salt-dependent lipase (BSDL). These complexes are secreted into the acinar lumen and diverted to the duodenal lumen. These fi ndings led us to investigate these enzyme-chaperone complexes in intestinal tissue. Grp94, Cpn60, and PDI are present on microvilli and on the endosom al compartment of enterocytes. Furthermore, we have shown that the Grp94-BS DL complexes are internalized by enterocytes through classical endocytosis. Upon dissociation of the BSDL-Grp94 complex in the late endosome, BSDL is transferred to the basolateral membrane. We propose that Grp94 interacts wi th specific receptors and/or could force the associated protein to adopt a specific conformation that allows its binding to corresponding membrane rec eptors and its internalization by enterocytes. These two hypotheses need no t to be exclusive. The existence of such a pancreatic secretion-intestinal absorption link speaks in favor of a coordinated functional connection betw een these two entities, through molecular chaperones, in order to optimize intestinal activities. Microsc. Res. Tech. 49:329-345, 2000. (C) 2000 Wiley -Liss, Inc.