Interaction of the Human Prostacyclin Receptor with Rab11

Reid, Helen M.; Mulvaney, Eamon P.; Turner, Elizebeth C.; Kinsella, B. Thérèse

doi:10.1074/jbc.m110.106476

Cited by 27 publications

(26 citation statements)

References 60 publications

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“…Hence, the temporal association and dissociation of PDZK1 with the hIP is a much more dynamic event, being largely regulated by phosphorylation/dephosphorylation, whereas the agonist-induced internalization of the hIP is a much slower event, requiring engagement and participation of the intracellular trafficking machinery, including members of the Rab GTPases, as we have previously reported (O'Keeffe et al , 2008; Wikstrom et al , 2008; Reid et al , 2010). Therefore, it is unlikely that there is a relationship between the temporal association between the hIP with PDZK1 and the processes regulating agonist-induced trafficking of the hIP.…”

Section: Discussionmentioning

confidence: 58%

Interaction of the human prostacyclin receptor with the PDZ adapter protein PDZK1: role in endothelial cell migration and angiogenesis

Turner

Mulvaney

Reid

et al. 2011

MBoC

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Section: Discussionmentioning

confidence: 58%

Interaction of the human prostacyclin receptor with the PDZ adapter protein PDZK1: role in endothelial cell migration and angiogenesis

Turner

Mulvaney

Reid

et al. 2011

MBoC

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“…We and others reported that an interaction between Rab proteins and GPCRs dictates the trafficking of the receptors (22)(23)(24)(25)(26)(27)(28)(29). However, whether other components of the Rab protein modification machinery or Rab effectors also interact with GPCRs remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Rab-mediated vesicular transport is well known to regulate membrane receptor trafficking, but less is known about whether membrane receptors conversely regulate the Rab-trafficking machinery. We and others showed that GPCRs interact with Rabs resulting in the regulation of receptor trafficking (22)(23)(24)(25)(26)(27)(28)(29). The task of unraveling whether membrane receptors interact with other elements of the Rab-associated machinery to direct their own trafficking remains.…”

Section: Previous Reports By Us and Others Demonstrated That G Proteimentioning

confidence: 99%

Regulation of β2-Adrenergic Receptor Maturation and Anterograde Trafficking by an Interaction with Rab Geranylgeranyltransferase

Lachance

Cartier

Génier

et al. 2011

Journal of Biological Chemistry

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Background:Interacting partners and regulation of Rab geranylgeranyltransferase are poorly characterized. Mechanisms of GPCR maturation and anterograde trafficking are not fully understood. Results: RGGTA interacts with a dileucine motif in the ␤ 2 AR to regulate ␤ 2 AR maturation/anterograde trafficking and ␤ 2 ARmediated Rab geranylgeranylation. Conclusion: RGGTA and the ␤ 2 AR interact functionally. Significance: This is the first demonstration of a functional interaction between RGGTA and a transmembrane receptor. Previous reports by us and others demonstrated that G protein-coupled receptors interact functionally with Rab GTPases.Here, we show that the ␤ 2 -adrenergic receptor (␤ 2 AR) interacts with the Rab geranylgeranyltransferase ␣-subunit (RGGTA). Confocal microscopy showed that ␤ 2 AR co-localizes with RGGTA in intracellular compartments and at the plasma membrane. Site-directed mutagenesis revealed that RGGTA binds to the L 339 L 340 motif in the ␤ 2 AR C terminus known to be involved in the transport of the receptor from the endoplasmic reticulum to the cell surface. Modulation of the cellular levels of RGGTA protein by overexpression or siRNA-mediated knockdown of the endogenous protein demonstrated that RGGTA has a positive role in the maturation and anterograde trafficking of the ␤ 2 AR, which requires the interaction of RGGTA with the ␤ 2 AR L 339 L 340 motif. Furthermore, the ␤ 2 AR modulates the geranylgeranylation of Rab6a, Rab8a, and Rab11a, but not of other Rab proteins tested in this study. Regulation of Rab geranylgeranylation by the ␤ 2 AR was dependent on the RGGTA-interacting L 339 L 340 motif. Interestingly, a RGGTA-Y107F mutant was unable to regulate Rab geranylgeranylation but still promoted ␤ 2 AR maturation, suggesting that RGGTA may have functions independent of Rab geranylgeranylation. We demonstrate for the first time an interaction between a transmembrane receptor and RGGTA which regulates the maturation and anterograde transport of the receptor, as well as geranylgeranylation of Rab GTPases.

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“…Often, however, removal leads to a lack of functionality in distal regions, such as those implicated in phosphorylation due to allosteric effects. For instance, it has been reported that (de-)palmitoylation of the human prostacyclin receptor occurs upon agonist binding, which therefore may provide a switch mechanism for structural changes in the proximity of the palmitoylated cysteines 24 . Additionally, the ability of the thyrotropin-releasing hormone receptor to become phosphorylated is severely inhibited by mutation of the palmitoylated cysteines 25 .…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics Simulations Reveal Specific Interactions of Post-translational Palmitoyl Modifications with Rhodopsin in Membranes

Olausson

Grossfield

Pitman³

et al. 2012

J. Am. Chem. Soc.

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We present a detailed analysis of the behavior of the highly flexible post-translational lipid modifications of rhodopsin from multiple-microsecond all-atom molecular dynamics simulations. Rhodopsin was studied in a realistic membrane environment that includes cholesterol, as well as saturated and polyunsaturated lipids with phosphocholine and phosphoethanolamine headgroups. The simulation reveals striking differences between the palmitoylations at Cys322 and Cys323 as well as between the palmitoyl chains and the neighboring lipids. Notably the palmitoyl group at Cys322 shows considerably greater contact with helix H1 of rhodopsin, yielding frequent chain upturns with longer reorientational correlation times, and relatively low order parameters. While the palmitoylation at Cys323 makes fewer protein contacts and has increased order compared to Cys322, it nevertheless exhibits greater flexibility with smaller order parameters than the stearoyl chains of the surrounding lipids. The dynamical structure of the palmitoylations—as well as their extensive fluctuations—suggests a complex function for the post-translational modifications in rhodopsin and potentially other G protein-coupled receptors, going beyond their role as membrane anchoring elements. Rather, we propose that the palmitoylation at Cys323 has a potential role as a lipid anchor, whereas the palmitoyl-protein interaction observed for Cys322 suggests a more specific interaction that affects the stability of the dark state of rhodopsin.

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Interaction of the Human Prostacyclin Receptor with Rab11

Cited by 27 publications

References 60 publications

Interaction of the human prostacyclin receptor with the PDZ adapter protein PDZK1: role in endothelial cell migration and angiogenesis

Interaction of the human prostacyclin receptor with the PDZ adapter protein PDZK1: role in endothelial cell migration and angiogenesis

Regulation of β2-Adrenergic Receptor Maturation and Anterograde Trafficking by an Interaction with Rab Geranylgeranyltransferase

Molecular Dynamics Simulations Reveal Specific Interactions of Post-translational Palmitoyl Modifications with Rhodopsin in Membranes

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