Localization of phospholipase Cbeta isozymes in the mouse cerebellum

To elucidate the role of phospholipase Cbeta (PLCbeta) isozymes in the cerebellum, the distributions of PLCbeta3 and PLCbeta4 were examined in wild-type and PLCbeta4-deficient mutant mice using immunohistochemistry, and the functions were evaluated by measurement of type 1 metabotropic glutamate receptor (mGluR1)-mediated inward current and Ca(2+) mobilization. In wild-type mice, PLCbeta4 was distributed equally in both rostral and caudal cerebellum, while PLCbeta3 was enriched in the caudal versus the rostral cerebellum. In PLCbeta4-deficient mice, there was no measurable inward current or intracellular Ca(2+) elevation in the rostral cerebellum, whereas small responses were observed in the caudal cerebellum. In wild-type mice, the inward current was observed only following the release of caged GTPgammaS, not caged IP(3). These results suggest that the signal transduction machinery, including receptors, G-proteins, PLCbeta3, PLCbeta4, and effectors, form a functional unit, and the deletion of PLCbeta4 alters this unit, markedly changing signal transduction efficacy.