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Mol Endocrinol. 2015 Aug;29(8):1095-106. doi: 10.1210/ME.2015-1065. Epub 2015 Jun 29.

Minireview: Spatial Programming of G Protein-Coupled Receptor Activity: Decoding Signaling in Health and Disease.

Author information

1
Institute of Reproductive Biology and Development, Department of Surgery and Cancer, Imperial College London, London, W12 0NN, United Kingdom.

Abstract

Probing the multiplicity of hormone signaling via G protein-coupled receptors (GPCRs) has demonstrated the complex signal pathways that underlie the multiple functions these receptors play in vivo. This is highly pertinent for the GPCRs key in reproduction and pregnancy that are exposed to cyclical and dynamic changes in their extracellular milieu. How such functional pleiotropy in GPCR signaling is translated to specific downstream cellular responses, however, is largely unknown. Emerging data strongly support mechanisms for a central role of receptor location in signal regulation via membrane trafficking. In this review, we discuss current progress in our understanding of the role membrane trafficking plays in location control of GPCR signaling, from organized plasma membrane signaling microdomains, potentially provided by both distinct endocytic and exocytic pathways, to more recent evidence for spatial control within the endomembrane system. Application of these emerging mechanisms in their relevance to GPCR activity in physiological and pathophysiological conditions will also be discussed, and in improving therapeutic strategies that exploits these mechanisms in order to program highly regulated and distinct signaling profiles.

PMID:
26121235
PMCID:
PMC5414706
DOI:
10.1210/ME.2015-1065
[Indexed for MEDLINE]
Free PMC Article

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