Localization of phospholipase C beta isozymes in the mouse cerebellum

To elucidate the role of phospholipase C beta (PLC beta) isozymes in the ce rebellum, the distributions of PLC beta 3 and PLC beta 4 were examined in w ild-type and PLC beta 4-deficient mutant mice using immunohistochemistry, a nd the functions were evaluated by measurement of type 1 metabotropic gluta mate receptor (mGluR1)-mediated inward current and Ca2+ mobilization, In wi ld-type mice, PLC beta 4 was distributed equally in both rostral and caudal cerebellum, while PLC beta 3 was enriched in the caudal versus the rostral cerebellum. In PLC beta 4-deficient mice, there was no measurable inward c urrent or intracellular Ca2+ elevation in the rostral cerebellum, whereas s mall responses were observed in the caudal cerebellum. In wild-type mice, t he inward current was observed only following the release of caged GTP gamm a S, not caged IP3. These results suggest that the signal transduction mach inery, including receptors, G-proteins, PLC beta 3, PLC beta 4, and effecte rs, form a functional unit, and the deletion of PLC beta 4 alters this unit , markedly changing signal transduction efficacy. (C) 1999 Academic Press.