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i5 rs w er *Author for correspondenceINTRODUCTION The involvement of small molecular mass GTP-binding proteins (small G-proteins) in the regulation of intracellular vesicular trafficking has been demonstrated using both genetic and biochemical approaches (Takai et al., 1992; Ferro-Novick and Jahn, 1994; Fischer von Mollard et al., 1994a). These proteins control the vesicular movement between ER and Golgi and within the Golgi complex (Takai et al., 1992; Ferro-Novick and Jahn, 1994; Fischer von Mollard et al., 1994a). A role for small G-proteins in exocytosis has also been proposed since, in yeast, one of these proteins (SEC4) is implicated in the targeting of post-Golgi secretory vesicles to the plasma membrane (Goud et al., 1988) and, in mammalian cells, small G-proteins have been localized on secretory granules (Darchen et al., 1990, 1995; Fischer von Mollard et al., 1990; Matteoli et al., 1991; Jena et al., 1994). Several lines of evidence make the members of the Rab3 family attractive candidates for the regulation of exocytosis in mammalian cells. First, Rab3A an Rab3C have been found on synaptic vesicles from which the have been shown to dissociate during exocytosis in a synapto somal preparation (Fischer von Mollard et al., 1991, 1994b Second, inhibition of Rab3B expression by anti-sense oligonu cleotides resulted in a decrease in Ca2+-stimulated secretio from pituitary cells (Lledo et al., 1993). Third, overexpressio of Rab3A mutant proteins defective in GTP hydrolysis or i guanine nucleotide binding inhibited exocytosis from neu roendocrine cells (Holz et al., 1994; Johannes et al., 1994 Fourth, a synthetic peptide mimicking the putative effecto binding domain of Rab3 proteins has been shown to affect exo cytosis from different secretory cell systems (Oberhauser et a