Scaffolding Protein in Ca2+ signaling

Abstract

Polarized expression of signaling complexes requires retention of the proteins in the microdomains, which expression and retention are aided by scaffolding proteins. Little or 1 m information is available as to the nature of scaffoldini: proteins in CaZ+ signaling in non-excitable cells. Recently 1 lomers are regarded as an attractive candidate of scaffoldin I : protein in Ca 2+ signaling, because Homers bind G protei . coupled receptors (GPCRs), IP3 receptors, ryanodinc receptors and TRP channels. However, their role in CaZ+ si: haling in vivo and in vitro is not known. The data suggested by our work using Homer knock-out mice demonstr ate a novel, unexpected function of Homer proteins, in that RGS proteins and PLCP GTPase Activatin;: activities are regulated and provide a molecular mechanis 1 a for tuning signal intensity generated by GPCRs and thus the characteristics of intracellualr CaZ+ oscillations. In addition, Homer protein facilitates a physical association between TRP channels and IP3 receptor that is required `Dr the TRP channel in response to signals, which provide t; .e evidence for a conformational coupling model with an e:;;ential role for interaction between TRP channels and intral ellular CaZ+ release channels.