PARTICIPATION OF GRP94-RELATED PROTEIN IN SECRETION OF PANCREATIC BILE SALT-DEPENDENT LIPASE AND IN ITS INTERNALIZATION BY THE INTESTINAL EPITHELIUM

In previous studies on the AR4-2J cell line, we have shown that secret ion of bile salt-dependent lipase (BSDL) involves a multiprotein compl ex, including a protein of 94 kDa (p94) that is immunologically relate d to the chaperone Grp94, which seems to play essential roles in the f olding process of BSDL, Combined biochemical and immunocytochemical in vestigations were carried out to study the secretion of BSDL by normal pancreatic cells and its transport to the small intestine where this enzyme is thought to exert its physiological function. Both BSDL and G rp94 antigenic sites were localized and found to be associated all alo ng the pancreatic acinar cell secretory pathway. Grp94 and BSDL remain associated from leaving the pancreas until arriving at the intestinal lumen. In pancreatic juice, both proteins appear as a complex of high molecular mass (180 kDa) containing at least one each of p94 and BSDL molecules, interacting by hydrophobic forces, At the intestinal level , associated Grp94 and BSDL were detected on microvilli and in the end osomal compartment of enterocytes. The BSDL mRNA, however, was not exp ressed by the intestinal mucosa, The pancreatic Grp94-BSDL complex was internalized through the endosomal compartment of enterocytes. Finall y, the two proteins dissociated in this compartment and BSDL, but not Grp94, was transferred to the basolateral membrane.