Impairment of bile salt-dependent lipase secretion in human pancreatic tumoral SOJ-6 cells

Bile salt-dependent lipase (BSDL) was detected in human SOJ-6 and rat AR4-2 J pancreatic cells. Whereas AR4-2J cells actively secreted the enzyme, BSDL was retained within the Golgi compartment of SOJ-6 cells. Because Rab6 is involved in vesicle transport in the Colgi apparatus and the trans-Golgi ne twork, we confirmed the presence of Rabb in these cells. In rat AR4-2J cell s, Rab6 as well as Rab1A/B and Rab2, partitioned between the cytosol and mi crosomes. In SOJ-6 cells Rab1A/B and Rab2 also partitioned between the cyto sol and microsomes, but Rab6 was strictly associated with microsome membran es, suggesting a specific defect of Rab6 cycling in human SOJ-6 cells. The apparent defect of cycling in these cells is not due to the expression of a defective Rab6 since its correct sequence was confirmed. We further demons trated that AR4-2J and SOJ-6 cells express the Ra6-GDI beta and Rab-GDI alp ha isoforms, respectively. However, the sequence of Rab-CDI beta, which may be the main form expressed by SOJ-6 cells, identified a few substitutions located in regions that are essential for Rab-GDI function. We conclude tha t the deficient secretion of BSDL by SOJ-6 cells could be due to the expres sion of defective Rab-GDI beta. In spite of the alterations in Rab-GDI beta , membrane proteins such as CD71 and NHE3 were correctly localized to the c ell plasma membrane of SOI-6 cells, suggesting that two junctional distinct secretory pathway coexist in pancreatic cells. (C) 2000 Wiley-Liss. Inc.