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Evolving View of Membrane Trafficking and Signaling Systems for G Protein-Coupled Receptors

  • Silvia Sposini
  • Aylin C. Hanyaloglu
Chapter
Part of the Progress in Molecular and Subcellular Biology book series (PMSB, volume 57)

Abstract

The G protein-coupled receptor (GPCR) superfamily activates complex signal pathways, yet untangling these signaling systems to understand how specificity in receptor signaling pathways is achieved, has been a challenging question. The roles of membrane trafficking in GPCR signal regulation has undergone a recent paradigm shift, from a mechanism that programs the plasma membrane G protein signaling profile to providing distinct signaling platforms critical for specifying receptor function in vivo. In this chapter, we discuss this evolution of our understanding in the endocytic trafficking systems employed by GPCRs, and how such systems play a deeply integrated role with signaling. We describe recent studies that suggest that the endomembrane compartment can provide a mechanism to both specify, and yet also diversify, GPCR signal transduction. These new evolving models could aid mechanistic understanding of complex disease and provide novel therapeutic avenues.

Abbreviations

AIP1

Actin-interacting protein 1

AKT (PKB)

Protein kinase B

ALIX

ALG-interacting protein X

AMSH

Associated molecule with the SH3 domain of STAM

AP2

Adaptor protein 2

APPL1

Adaptor protein containing PH domain, PTB domain, and leucine zipper motif

ARRDC

Arresting domain containing

Β1AR, B2AR

Beta adrenergic receptor 1 or 2

CB1

Cannabinoid receptor 1

CCP

Clathrin-coated pit

CXCR4

Chemokine receptor 4

DOR

δ-opioid receptor

EE

Early endosome

EGF

Epidermal growth factor

EGFR

EGF receptor

EPB 50

ERM-binding phosphoprotein 50

ERM

Ezrin–radixin–moesin

ESCRT

Endosomal sorting complex required for transport

GAP

GTPase-activating protein

GASP-1

GPCR-associated sorting protein-1

GDP

Guanosine diphosphate

GEF

GDP exchange factor

GIPC

Gαi-interacting protein C-terminus

GPCR

G protein-coupled receptors

GRK

GPCR kinase

GSK3

Glycogen synthase kinase 3

GTP

Guanosine triphosphate

HGF

Hepatocyte growth factor

Hrs

HGF-regulated tyrosine kinase substrate

LHR

Luteinizing hormone receptor

MOR

μ-opioid receptor

MVB

Multivesicular body

PAR

Protease-activated receptor

PDZ

Post-synaptic density 95/disk large/zonula occludens-1

PI3P

Phosphatidylinositol-3 phosphate

PKA

Protein kinase A

PKC

Protein kinase C

PSD

Post-synaptic density protein 95

PTHR

Parathyroid hormone receptor

RGS

Regulator of G protein signaling

SNX27

Sorting nexin 27

STAM

Signal-transducing adaptor protein

STAT

Signal transducer and activator of transcription

TAB1

TGF-beta-activated kinase 1-binding protein

TGN

Trans-Golgi network

TM

Transmembrane

TSHR

Thyroid-stimulating hormone receptor

UBD

Ubiquitin-binding domain

UBPY

Ubiquitin-specific processing protease Y

V2R

V2 vasopressin receptor

VASP

Vasodilator-stimulated phosphoprotein

VEE

Very early endosome

Vps

Vacuolar protein sorting

WASH

Wiskott–Aldrich syndrome protein and SCAR homolog

Wnt

Wingless-related integration site

Notes

Acknowledgements

This work was supported by grants from the Wellcome Trust (WT085099MA), Genesis Research Trust (P15844) to A.C.H, and an Imperial College London President’s Scholarship to S.S.

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Reproductive and Developmental Biology, Department of Surgery and CancerHammersmith Campus, Imperial College LondonLondonUK

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