Regulation of G Protein-Coupled Receptor Function by Na<sup>+</sup>/H<sup>+</sup>Exchange Regulatory Factors

Ardura, Juan A.; Friedman, Peter A.

doi:10.1124/pr.110.004176

Cited by 95 publications

(107 citation statements)

References 183 publications

Supporting

Mentioning

104

Contrasting

Order By: Relevance

“…The majority of previous studies have reported a role for NHERF1 in the regulation of receptor signaling, recycling, or stabilization at the cell membrane (24,35). Studies with the thromboxane (20), adenosine A2B (21), and the PTH1R (7,30,36) have also described a regulatory role for NHERF1 in GPCR internalization, however, these studies have all reported an inhibitory effect of NHERF1 on receptor internalization.…”

Section: Discussionmentioning

confidence: 99%

Arrestin Scaffolds NHERF1 to the P2Y12 Receptor to Regulate Receptor Internalization

Nisar¹,

Cunningham²,

Saxena

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The PDZ-binding motif of the P2Y 12 receptor regulates correct receptor traffic in human platelets. Results: The PDZ-binding protein NHERF1 binds to the P2Y 12 receptor to promote agonist-dependent internalization. Conclusion: Arrestin scaffolds NHERF1 to the P2Y 12 receptor to facilitate effective NHERF1-dependent receptor internalization. Significance: A novel model of arrestin-dependent GPCR internalization.

show abstract

Section: Discussionmentioning

confidence: 99%

Arrestin Scaffolds NHERF1 to the P2Y12 Receptor to Regulate Receptor Internalization

Nisar¹,

Cunningham²,

Saxena

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Na 1 /H 1 Exchanger Regulatory Factor 2. The topology of Na 1 /H 1 exchanger regulatory factor 2 (NHERF2) is quite similar to NHERF1 as it shares a 44% sequence homology with NHERF1 and contains two PDZ domains and a carboxylterminal ezrin-binding domain (Ardura and Friedman, 2011) (Fig. 2).…”

Section: Membrane-associated Guanylate Kinase With Inverted Orientatimentioning

confidence: 99%

PDZ Protein Regulation of G Protein–Coupled Receptor Trafficking and Signaling Pathways

Dunn

Ferguson

2015

Mol Pharmacol

View full text Add to dashboard Cite

G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins, postsynaptic density protein of 95 kilodaltons, disc large, zona occludens-1 (PDZ) domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms. PDZ proteins play an important role in regulating receptor and channel protein localization within synapses and tight junctions and function to scaffold intracellular signaling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs and provide insight into the potential mechanisms of action. These PDZ domain-containing proteins include the membraneassociated guanylate-like kinases [postsynaptic density protein of 95 kilodaltons; synapse-associated protein of 97 kilodaltons; postsynaptic density protein of 93 kilodaltons; synapse-associated protein of 102 kilodaltons; discs, large homolog 5; caspase activation and recruitment domain and membrane-associated guanylate-like kinase domain-containing protein 3; membrane protein, palmitoylated 3; calcium/calmodulin-dependent serine protein kinase; membrane-associated guanylate kinase protein (MAGI)-1, MAGI-2, and MAGI-3], Na 1 /H 1 exchanger regulatory factor proteins (NHERFs) (NHERF1, NHERF2, PDZ domaincontaining kidney protein 1, and PDZ domain-containing kidney protein 2), Golgi-associated PDZ proteins (Ga-binding protein interacting protein, C-terminus and CFTR-associated ligand), PDZ domain-containing guanine nucleotide exchange factors (GEFs) 1 and 2, regulator of G protein signaling (RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and leukemia-associated RhoGEF), RGS3 and RGS12, spinophilin and neurabin-1, SRC homology 3 domain and multiple ankyrin repeat domain (Shank) proteins (Shank1, Shank2, and Shank3), partitioning defective proteins 3 and 6, multiple PDZ protein 1, Tamalin, neuronal nitric oxide synthase, syntrophins, protein interacting with protein kinase C a 1, syntenin-1, and sorting nexin 27.

show abstract

“…Some NHE-RFs have a Cterminal binding domain that connects them to the cytoskeleton, suggesting a role in sensing cytoskeletal modifications and, by extension, cell volume (Thelin et al, 2005). Given the difference in molecular mass between the isoforms (13kDa), they may present different orthologs rather than PTMs (Ardura and Friedman, 2011).…”

Section: Cytoskeletal Modifications and Vesicular Transportmentioning

confidence: 99%

“…NHE-RF can be phosphorylated by protein kinase A and affects the signaling of G-protein coupled receptors in addition to transporters (e.g. Na + /H + exchanger), ion exchangers and signaling proteins (Ardura and Friedman, 2011). Some NHE-RFs have a Cterminal binding domain that connects them to the cytoskeleton, suggesting a role in sensing cytoskeletal modifications and, by extension, cell volume (Thelin et al, 2005).…”

Section: Cytoskeletal Modifications and Vesicular Transportmentioning

confidence: 99%

Proteomics of hyposaline stress in blue mussel congeners (genusMytilus): implications for biogeographic range limits in response to climate change

Tomanek

Zuzow

Hitt

et al. 2012

Journal of Experimental Biology

View full text Add to dashboard Cite

SUMMARYClimate change is affecting speciesʼ physiology, pushing environmental tolerance limits and shifting distribution ranges. In addition to temperature and ocean acidification, increasing levels of hyposaline stress due to extreme precipitation events and freshwater runoff may be driving some of the reported recent range shifts in marine organisms. Using two-dimensional gel electrophoresis and tandem mass spectrometry, we characterized the proteomic responses of the cold-adapted blue mussel Mytilus trossulus, a native to the Pacific coast of North America, and the warm-adapted M. galloprovincialis, a Mediterranean invader that has replaced the native from the southern part of its range, but may be limited from expanding north due to hyposaline stress. After exposing laboratory-acclimated mussels for 4h to two different experimental treatments of hyposaline conditions and one control treatment (24.5, 29.8 and 35.0psu, respectively) followed by a 0 and 24h recovery at ambient salinity (35psu), we detected changes in the abundance of molecular chaperones of the endoplasmic reticulum (ER), indicating protein unfolding, during stress exposure. Other common responses included changes in small GTPases of the Ras superfamily during recovery, which suggests a role for vesicle transport, and cytoskeletal adjustments associated with cell volume, as indicated by cytoskeletal elements such as actin, tubulin, intermediate filaments and several actin-binding regulatory proteins. Changes of proteins involved in energy metabolism and scavenging of reactive oxygen species suggest a reduction in overall energy metabolism during recovery. Principal component analyses of protein abundances suggest that M. trossulus is able to respond to a greater hyposaline challenge (24.5psu) than M. galloprovincialis (29.8psu), as shown by changing abundances of proteins involved in protein chaperoning, vesicle transport, cytoskeletal adjustments by actin-regulatory proteins, energy metabolism and oxidative stress. While proteins involved in energy metabolism were lower in M. trossulus during recovery from hyposaline stress, M. galloprovincialis showed higher abundances of those proteins at 29.8psu, suggesting an energetic constraint in the invader but not the native congener. Both species showed lower levels of oxidative stress proteins during recovery. In addition, oxidative stress proteins associated with protein synthesis and folding in the ER showed lower levels during recovery in M. galloprovincialis, in parallel with ER chaperones, indicating a reduction in protein synthesis. These differences may enable the native M. trossulus to cope with greater hyposaline stress in the northern part of its range, as well as to outcompete M. galloprovincialis in the southern part of M. trossulusʼ range, thereby preventing M. galloprovincialis from expanding further north. Supplementary material available online at

show abstract

Regulation of G Protein-Coupled Receptor Function by Na⁺/H⁺Exchange Regulatory Factors

Cited by 95 publications

References 183 publications

Arrestin Scaffolds NHERF1 to the P2Y12 Receptor to Regulate Receptor Internalization

Arrestin Scaffolds NHERF1 to the P2Y12 Receptor to Regulate Receptor Internalization

PDZ Protein Regulation of G Protein–Coupled Receptor Trafficking and Signaling Pathways

Proteomics of hyposaline stress in blue mussel congeners (genusMytilus): implications for biogeographic range limits in response to climate change

Contact Info

Product

Resources

About

Regulation of G Protein-Coupled Receptor Function by Na+/H+Exchange Regulatory Factors

Cited by 95 publications

References 183 publications

Arrestin Scaffolds NHERF1 to the P2Y12 Receptor to Regulate Receptor Internalization

Arrestin Scaffolds NHERF1 to the P2Y12 Receptor to Regulate Receptor Internalization

PDZ Protein Regulation of G Protein–Coupled Receptor Trafficking and Signaling Pathways

Proteomics of hyposaline stress in blue mussel congeners (genusMytilus): implications for biogeographic range limits in response to climate change

Contact Info

Product

Resources

About

Regulation of G Protein-Coupled Receptor Function by Na⁺/H⁺Exchange Regulatory Factors