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This Article Accepted manuscript (PDF) All Versions of this Article: JME-10-0014v1 45/1/1    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Calebiro, D. Articles by Lohse, M. PubMed PubMed Citation Articles by Calebiro, D. Articles by Lohse, M.

D Calebiro, Rudolf Virchow Center, Wuerzburg, Germany
V Nikolaev, Rudolf Virchow Center, Wuerzburg, Germany
M Lohse, Rudolf Virchow Center, Wuerzburg, Germany

Correspondence: Davide Calebiro, Email: davide.calebiro{at}toxi.uni-wuerzburg.de

Abstract

G protein-coupled receptors (GPCRs) are the largest family of plasma membrane receptors. They mediate the effects of several endogenous cues and serve as important pharmacological targets. Although many biochemical events involved in GPCR-signaling have been characterized in great detail, little is known about their spatiotemporal dynamics in living cells. The recent advent of optical methods based on fluorescent resonance energy transfer allows, for the first time, to monitor directly GPCR-signaling in living cells. Utilizing these methods it was recently possible to show that the receptors for two protein/peptide hormones, the thyroid stimulating hormone and the parathyroid hormone, continue signaling to cyclic AMP after their internalization into endosomes. This type of intracellular signaling is persistent and apparently triggers specific cellular outcomes. Here we review these recent data and explain the optical methods used for such studies. Based on these findings, we propose a revision of the current model of the GPCR-cAMP signaling pathway to accommodate receptor signaling at endosomes.