INHIBITION OF RAB3B EXPRESSION ATTENUATES CA2-DEPENDENT EXOCYTOSIS INRAT ANTERIOR-PITUITARY-CELLS()

LOW-MOLECULAR-WEIGHT GTP-binding proteins (small G proteins) of the Ra b family have been proposed to act as central regulators of vesicular traffic1,2, and proteins of the Rab3 subfamily (Rab3A, B, C and D)3-6 are thought to be,associated with membrane vesicles or granules underg oing exocytotic fusion with the plasma membrane7-10. Rab3A is highly e xpressed in brain11, whereas Rab3B is the major form found in rat ante rior pituitary gland. We report here that antisense oligonucleotides a gainst Rab3B, introduced into pituitary cells using the whole-cell pat ch clamp technique, specifically and reversibly block expression of Ra b3B. We find that calcium-dependent exocytosis is inhibited without af fecting endocytosis. Antisense oligonucleotides directed against Rab3A have no effect. Our results indicate that Rab3B is likely to be a key intracellular signalling molecule which can control exocytosis downst ream of other calcium-dependent processes in anterior pituitary cells.