Synergistic Ca2+ Responses by Gαi- and Gαq-coupled G-protein-coupled Receptors Require a Single PLCβ Isoform That Is Sensitive to Both Gβγ and Gαq

Robert A Rebres,Tamara I.A Roach,Iain D.C Fraser,Finly Philip,Christina Moon,Keng-Mean Lin,Jamie Liu,Leah Santat,Lucas Cheadle,Elliott M Ross,Melvin I Simon,William E Seaman

doi:10.1074/jbc.m110.198200

Abstract

Synergistic Ca2+ Responses by Gαi- and Gαq-coupled G-protein-coupled Receptors Require a Single PLCβ Isoform That Is Sensitive to Both Gβγ and Gαq

Highlights

Cross-talk between G␣i- and G␣q-linked G-protein-coupled receptors yields synergistic Ca2؉ responses in a variety of cell types
Because phospholipase C (PLC)␤4 appears to have an inhibitory role and PLC␤1 is not expressed in macrophages, the residual Ca2ϩ synergy in phospholipase C␤3 (PLC␤3)-deficient macrophages was thought to depend on PLC␤2 [11]
PLC␤2, like PLC␤3, has the capacity to mediate synergy in these cells. Both the G␤␥ and G␣q Binding Sites of PLC␤3 Are Required for Synergistic Ca2ϩ Responses—PLC␤3 is responsive to both G␤␥ and G␣q, and our studies suggest that synergy by G␣i and G␣q GPCRs may be mediated by the combined action of G␤␥ and G␣q on a single PLC␤ isoform

Summary

Introduction

Cross-talk between G␣i- and G␣q-linked G-protein-coupled receptors yields synergistic Ca2؉ responses in a variety of cell types. Macrophages Deficient in Both PLC␤2 and PLC␤3 Have No Synergistic Ca2ϩ Response to C5a and UDP—Synergy in Ca2ϩ signaling in macrophages between C5a, acting on the G␣icoupled C5aR, and UDP, acting on G␣q-coupled P2Y receptors, was previously found to be primarily dependent on expression of PLC␤3, but some synergy remained in PLC␤3-deficient cells [11].

Results

Conclusion