Rab3a effectors in acrosomal exocytosis

BELLO, OSCAR D.; MAYORGA, LUIS S.

Mar del Plata, Buenos Aires, Republica Argentina

Congreso; SAIB XLIII; 2007

Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular

Rab3A is a monomeric GTPase required for regulated exocytosis. However, the detailed mechanism of Rab3A action is not completely understood. Previous results from our laboratory indicate that Rim is a Rab3A effector in acrosomal exocytosis. Recent experiments have shown that Munc13, a Rim interacting protein participates in this process. The ZF domain of Rim2 (residues 82-142, which binds Rab3Aand Munc13) and MuncC2A (Rim-binding domain of Munc13) strongly affected exocytosis in SLO permeabilized sperm. Interestingly, the inhibitory effect of MuncC2A was competed by the Rim ZF wild type domain but not by a Munc13 binding-defective mutant (K97E / K99E). The antiMuncC2A antibody recognized the endogenous protein in the sperm acrosomal region, and inhibited acrosomal exocytosis. By using a non prenylated RabGTP S and a light-sensitive calcium chelator we demonstrated that Munc13 and Rim affect the Rab3A dependent stage of the acrosomal exocytosis. Taken together our data support a model where Munc13 directly interacts with Nterminal domain of Rim, and this interaction is required for the role of Rim as Rab3Aeffector in acrosomal exocytosis