G protein-dependent Ca2+ signaling complexes in polarized cells

S. Muallem, T. M. Wilkie

Research output: Contribution to journalReview articlepeer-review

45 Scopus citations


Polarized cells signal in a polarized manner. This is exemplified in the patterns of [Ca2+](i) waves and [Ca2+](i) oscillations evoked by stimulation of G protein-coupled receptors in these cells. Organization of Ca2+-signaling complexes in cellular microdomains, with the aid of scaffolding proteins, is likely to have a major role in shaping G protein-coupled [Ca2+](i) signal pathways. In epithelial cells, these domains coincide with sites of [Ca2+](i)-wave initiation and local [Ca2+](i) oscillations. Cellular microdomains enriched with Ca2+-signaling proteins have been found in several cell types. Microdomains organize communication between Ca2+-signaling proteins in the plasma membrane and internal Ca2+ stores in the endoplasmic reticulum through the interaction between the IP3 receptors in the endoplasmic reticulum and Ca2+-influx channels in the plasma membrane. Ca2+ signaling appears to be controlled within the receptor complex by the regulators of G protein-signaling (RGS) proteins. Three domains in RGS4 and related RGS proteins contribute important regulatory features. The RGS domain accelerates GTP hydrolysis on the Gα subunit to uncouple receptor stimulation from IP3 production; the C-terminus may mediate interaction with accessory proteins in the complex; and the N-terminus acts in a receptor-selective manner to confer regulatory specificity. Hence, RGS proteins have both catalytic and scaffolding function in Ca2+ signaling. Organization of Ca2+-signaling proteins into complexes within microdomains is likely to play a prominent role in the localized control of [Ca2+](i) and in [Ca2+](i) oscillations.

Original languageEnglish (US)
Pages (from-to)173-180
Number of pages8
JournalCell Calcium
Issue number5
StatePublished - Nov 1999

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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