Distinct G protein–coupled receptor recycling pathways allow spatial control of downstream G protein signaling

Bowman, Shanna L.; Shiwarski, Daniel J.; Puthenveedu, Manojkumar A.

doi:10.1083/jcb.201512068

Cited by 74 publications

(91 citation statements)

References 51 publications

(83 reference statements)

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“…Receptor phosphorylation begins at the plasma membrane independent of endocytosis, and at least some phosphorylation is present on receptors throughout post‐endocytic trafficking . Receptor phosphorylation is important for post‐endocytic trafficking and for endosomal receptor signaling . Modulating GPCR ubiquitination is another potential target of endocytic lifetime regulation.…”

Section: Agonist‐mediated Receptor Endocytosismentioning

confidence: 99%

Regulation of G protein‐coupled receptor signaling by plasma membrane organization and endocytosis

Weinberg

Puthenveedu

2019

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The trafficking of G protein coupled‐receptors (GPCRs) is one of the most exciting areas in cell biology because of recent advances demonstrating that GPCR signaling is spatially encoded. GPCRs, acting in a diverse array of physiological systems, can have differential signaling consequences depending on their subcellular localization. At the plasma membrane, GPCR organization could fine‐tune the initial stages of receptor signaling by determining the magnitude of signaling and the type of effectors to which receptors can couple. This organization is mediated by the lipid composition of the plasma membrane, receptor‐receptor interactions, and receptor interactions with intracellular scaffolding proteins. GPCR organization is subsequently changed by ligand binding and the regulated endocytosis of these receptors. Activated GPCRs can modulate the dynamics of their own endocytosis through changing clathrin‐coated pit dynamics, and through the scaffolding adaptor protein β‐arrestin. This endocytic regulation has signaling consequences, predominantly through modulation of the MAPK cascade. This review explores what is known about receptor sorting at the plasma membrane, protein partners that control receptor endocytosis, and the ways in which receptor sorting at the plasma membrane regulates downstream trafficking and signaling.

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Section: Agonist‐mediated Receptor Endocytosismentioning

confidence: 99%

Regulation of G protein‐coupled receptor signaling by plasma membrane organization and endocytosis

Weinberg

Puthenveedu

2019

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“…Another example is that of AQP2 which is constitutively inserted into the apical membrane of collecting ducts upon mutating its PKA target Ser 256 to aspartic acid [53]. Finally, mutating the two PKA-target serines in the C-tail of the ß 2 -AR to aspartic acid, altered its trafficking roadmap from that of the “sequence-dependent’ pathway into the “sequence-independent” pathway [69]. …”

Section: Role Of Post-translational Modifications By Compartmentalmentioning

confidence: 99%

“…The FKBP15 protein consists of at least four domains, a N-terminal WASP homology 1 domain [69-171], FKBP-like [178-290], coiled coil [∼500-∼950] and C-terminal acidic end [∼985-1200] domains [132] and Fig. 3D.…”

Section: Mechanism Of Barcode-mediated Sorting Of the Gpcr In Earmentioning

confidence: 99%

“…PBM- and ASRT-independent manner). These GPCR correspond to non-PDZ recycling sequences derived from the μ-opioid or dopamine1-R that are fused to the C-tail of the ß 1 -AR and include the (S312D) ß 1 -AR point mutant and the (Ser 345/346 to Asp) ß 2 -AR double mutant [69, 160]. These GPCR or their modified point mutants or chimeras might traffic by geometric sorting via the “bulk” pathway involved in trafficking of Tfr and LDL receptors and others [69, 110], but that assumption still lacks experimental proof.…”

Section: A Framework Depicting the Various Gpcr Trafficking Roadmapsmentioning

confidence: 99%

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Barcoding of GPCR trafficking and signaling through the various trafficking roadmaps by compartmentalized signaling networks

Bahouth

Nooh

2017

Cellular Signalling

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Proper signaling by G protein coupled receptors (GPCR) is dependent on the specific repertoire of transducing, enzymatic and regulatory kinases and phosphatases that shape its signaling output. Activation and signaling of the GPCR through its cognate G protein is impacted by G protein-coupled receptor kinase (GRK)-imprinted “barcodes” that recruit ß-arrestins to regulate subsequent desensitization, biased signaling and endocytosis of the GPCR. The outcome of agonist-internalized GPCR in endosomes is also regulated by sequence motifs or “barcodes” within the GPCR that mediate its recycling to the plasma membrane or retention and eventual degradation as well as its subsequent signaling in endosomes. Given the vast number of diverse sequences in GPCR, several trafficking mechanisms for endosomal GPCR have been described. The majority of recycling GPCR, are sorted out of endosomes in a “sequence-dependent pathway” anchored around a type-1 PDZ-binding module found in their C-tails. For a subset of these GPCR, a second “barcode” imprinted onto specific GPCR serine/threonine residues by compartmentalized kinase networks was required for their efficient recycling through the “sequence-dependent pathway”. Mutating the serine/threonine residues involved, produced dramatic effects on GPCR trafficking, indicating that they played a major role in setting the trafficking itinerary of these GPCR. While endosomal SNX27, retromer/WASH complexes and actin were required for efficient sorting and budding of all these GPCR, additional proteins were required for GPCR sorting via the second “barcode”. Here we will review recent developments in GPCR trafficking in general and the human ß1-adrenergic receptor in particular across the various trafficking roadmaps. In addition, we will discuss the role of GPCR trafficking in regulating endosomal GPCR signaling, which promote biochemical and physiological effects that are distinct from those generated by the GPCR signal transduction pathway in membranes.

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“…These data suggest the involvement of different internalization processes and that these receptors might move to different cellular locations (i. e., different endosomal compartments). There is already published information indicating that GPCRs might internalize into different compartments under different conditions (see, for example and references therein).…”

Section: Resultsmentioning

confidence: 99%

Free fatty acid receptor 4 agonists induce lysophosphatidic acid receptor 1 (LPA₁) desensitization independent of LPA₁ internalization and heterodimerization

et al. 2018

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The crosstalk between the free fatty acid receptor FFA4 and the lysophosphatidic acid receptor LPA seems to be of pathophysiological importance. We explored this crosstalk employing co-expression of fluorescent protein-tagged receptors. FFA4 activation induces functional desensitization of LPA receptors and phosphorylation of both receptors. LPA activation induces phosphorylation of LPA , but not of FFA4, and induces internalization of both receptors into heterogeneous types of vesicles. Docosahexaenoic acid (DHA) induces internalization of FFA4 but not of LPA . Fatty acid-induced FFA4-LPA interaction was observed using Förster resonance energy transfer and co-immunoprecipitation. Such interaction took place after desensitization was already established. Data indicate that FFA4 activation induces LPA desensitization in an internalization-independent process and that complex cellular processes participate in the crosstalk of these receptors.

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Distinct G protein–coupled receptor recycling pathways allow spatial control of downstream G protein signaling

Abstract: GPCRs can activate different programs of gene expression from the plasma membrane and the endosome. Bowman et al. show that signaling by endosomal β-2 adrenergic receptors occurs at the microdomains that GPCRs use for sequence-dependent recycling.

Cited by 74 publications

References 51 publications

Regulation of G protein‐coupled receptor signaling by plasma membrane organization and endocytosis

Regulation of G protein‐coupled receptor signaling by plasma membrane organization and endocytosis

Barcoding of GPCR trafficking and signaling through the various trafficking roadmaps by compartmentalized signaling networks

Free fatty acid receptor 4 agonists induce lysophosphatidic acid receptor 1 (LPA₁) desensitization independent of LPA₁ internalization and heterodimerization

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Distinct G protein–coupled receptor recycling pathways allow spatial control of downstream G protein signaling

Abstract: GPCRs can activate different programs of gene expression from the plasma membrane and the endosome. Bowman et al. show that signaling by endosomal β-2 adrenergic receptors occurs at the microdomains that GPCRs use for sequence-dependent recycling.

Cited by 74 publications

References 51 publications

Regulation of G protein‐coupled receptor signaling by plasma membrane organization and endocytosis

Regulation of G protein‐coupled receptor signaling by plasma membrane organization and endocytosis

Barcoding of GPCR trafficking and signaling through the various trafficking roadmaps by compartmentalized signaling networks

Free fatty acid receptor 4 agonists induce lysophosphatidic acid receptor 1 (LPA1) desensitization independent of LPA1 internalization and heterodimerization

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Product

Resources

About

Free fatty acid receptor 4 agonists induce lysophosphatidic acid receptor 1 (LPA₁) desensitization independent of LPA₁ internalization and heterodimerization