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.
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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
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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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Sposini, S., Hanyaloglu, A.C. (2018). Evolving View of Membrane Trafficking and Signaling Systems for G Protein-Coupled Receptors. In: Lamaze, C., Prior, I. (eds) Endocytosis and Signaling. Progress in Molecular and Subcellular Biology, vol 57. Springer, Cham. https://doi.org/10.1007/978-3-319-96704-2_10
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