Cerebellar β2-chimaerin, a GTPase-activating protein for p21 Ras-related Rac is specifically expressed in granule cells and has a unique N-terminal SH2 domain

Abstract

β-Chimaerin, a 30-kDa GTPase-activating protein (GAP) for the p21 Ras- related Rac, is expressed specifically in late stage spermatocytes (Leung, T., How, B.-E., Manser, E., and Lim, L. (1993) J. Biol. Chem. 268, 3813- 3816). Using antibodies raised against β-chimaerin, we detected a major 46- kDa RacGAP in the rat cerebellum. With β-chimaerin cDNA as a probe and using polymerase chain reaction, cDNAs from both human and rat cerebellum were isolated. The human and rat cDNAs encoded sequences containing cysteine-rich and GAP domains identical to those of testis β-chimaerin. The cDNAs also encoded an additional N-terminal SH2 (Src homology 2) domain, probably derived from the β-chimaerin gene by alternate splicing. This SH2 domain of the predicted 54-kDa protein was strikingly similar to that of α2-chimaerin, including replacement by glutamic acid of the invariant tryptophan present at the start of other SH2 domains. The SH2 domains of α- and β-chimaerin thus represent a subset of SH2 domains. The cerebellar β-chimaerin (β2-) is expressed mainly in granule cells and exhibits postnatal developmental increases. β2-Chimaerin was enriched in particulate/synaptosomal fractions. In the mouse weaver mutant lacking mature granule cells, there is a corresponding decrease in β2-chimaerin, which could well serve as a marker of granule cell differentiation.