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 AR4-2J 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 Golgi apparatus and the trans-Golgi network, we confirmed the presence of Rab6 in these cells. In rat AR4-2J cells, Rab6 as well as Rab1A/B and Rab2, partitioned between the cytosol and microsomes. In SOJ-6 cells Rab1A/B and Rab2 also partitioned between the cytosol and microsomes, but Rab6 was strictly associated with microsome membranes, 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 demonstrated that AR4-2J and SOJ-6 cells express the Rab-GDIbeta and Rab-GDIalpha isoforms, respectively. However, the sequence of Rab-GDIbeta, 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 that the deficient secretion of BSDL by SOJ-6 cells could be due to the expression of defective Rab-GDIbeta. In spite of the alterations in Rab-GDIbeta, membrane proteins such as CD71 and NHE3 were correctly localized to the cell plasma membrane of SOJ-6 cells, suggesting that two functional distinct secretory pathway coexist in pancreatic cells.
Caillol
N
N
INSERM Unité 260-Faculté de Médecine-Timone, 27 bld Jean Moulin, 13385 Marseille cedex 05 France.
Pasqualini
E
E
Lloubes
R
R
Lombardo
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001647:Bile Acids and Salts / Q000378:metabolism; D001693:Biological Transport, Active; D017931:DNA Primers / Q000235:genetics; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D001647:Bile Acids and Salts; D017931:DNA Primers; C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C094135:Rab6 protein; C054784:bile salt-stimulated lipase; D002787:Sterol Esterase; D020691:rab GTP-Binding Proteins