CHAPERONE FUNCTION OF A GRP 94-RELATED PROTEIN FOR FOLDING AND TRANSPORT OF THE PANCREATIC BILE SALT-DEPENDENT LIPASE

In its fundamental attributes, the secretion pathway of the pancreatic bile salt-dependent lipase (BSDL) followed that described for all enz ymes involved in regulated secretion. This route was inhibited by drug s that affect protein synthesis and intracellular transport. In the pr esence of monensin, BSDL was solely detected in microsome membrane fra ctions. The association of BSDL with intracellular membranes involved a protein complex, formed by at least two proteins of 94 and 56 kDa. I n cells experiencing the metabolic stress due to azetidine-2-carboxyli c acid, BSDL was additionally associated with a protein of 46 kDa. Aff inity blotting showed that BSDL bound directly to the 94-kDa protein ( p94). It was suggested that p94 could be a molecular chaperone, furthe r identified as related to the 94-kDa glucose regulated protein (Grp 9 4). The membrane-associated BSDL (i.e. BSDL bound to the Grp 94-relate d p94) was O- and N-glycosylated and consequently appeared released fr om membranes in the trans-Golgi compartment. Therefore and for the fir st time, it is suggested that a multiprotein complex including the cha perone Grp 94-related p94 protein may play an essential role in the fo lding and transport of BSDL. One hypothesis is that the association of BSDL with membrane via the Grp 94-related p94 along its secretion pat hway is required for its complete O-glycosylation, which occurs on the extended mucin-like structures present on the C-terminal part of the protein.