The G protein-coupled receptor associated sorting protein GASP-1 regulates the signaling and trafficking of the viral chemokine receptor US28

Tschische, Pia; Moser, Elisabeth; Thompson, Dawn; Vischer, Henry F.; Parzmair, Gerald P.; Platzer, Wolfgang; Schaider, Helmut; Smit, Martine J.; Martini, Lene; Whistler, Jennifer L.; Waldhoer, Maria

doi:10.1111/j.1600-0854.2010.1045.x

Cited by 7 publications

(17 citation statements)

References 27 publications

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“…In addition, we observed that the overexpression of GASP-1 in HEK293 cells significantly enhanced the G ␣ q /phospholipase C/inositol phosphate turnover by US28, whereas shRNA silencing of GASP-1 dramatically reduced inositol phosphate formation in these cells [44] . Moreover, the activation of the transcription factors nuclear factor-B and cyclic-AMP-responsive element-binding protein via US28 were also either enhanced or prevented by overexpression or shRNA silencing of GASP-1, respectively [44] . It is not clear yet whether the enhanced/decreased signaling capacity of US28 in the presence/absence of GASP-1 is caused by (i) a more active conformational state of the receptor upon GASP-1 binding, or (ii) its relocalization into a particular endosomal compartment that is important for signal transduction [51,52] .…”

Section: Gasp-1: Regulator Of Signal Transduction?mentioning

confidence: 75%

Section: Gasp-1: Regulator Of Signal Transduction?mentioning

confidence: 99%

“…GASP-1 targets the virally encoded 7TM-GPCR US28 to late endosomes/lysosomes [44] , a place that has been suggested to be crucial for the envelopment of viruses. In addition, we observed that the overexpression of GASP-1 in HEK293 cells significantly enhanced the G ␣ q /phospholipase C/inositol phosphate turnover by US28, whereas shRNA silencing of GASP-1 dramatically reduced inositol phosphate formation in these cells [44] . Moreover, the activation of the transcription factors nuclear factor-B and cyclic-AMP-responsive element-binding protein via US28 were also either enhanced or prevented by overexpression or shRNA silencing of GASP-1, respectively [44] .…”

Section: Gasp-1: Regulator Of Signal Transduction?mentioning

confidence: 99%

“…For instance, the DOR-GASP-1 interaction is disrupted by overexpression of dominant negative cGASP-1 [7] , which inhibits the traf- ficking of DOR to lysosomes and promotes its recycling back to the cell surface [7] . GASP-2, with the closest homology to GASP-1, has been shown to directly bind the D 2 dopamine receptor (D2R) and the ␤ 2 -AR [29] , the viral chemokine receptor US28 [44] as well as huntingtin (Htt), a protein playing a role in the neurodegenerative disorder Huntington's disease [50] ( table 2 ). However, to date no functional consequence has been reported for protein interactions with GASP-2.…”

Section: Postendocytic Sorting Of 7tm-gpcrsmentioning

confidence: 99%

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G Protein-Coupled Receptor-Associated Sorting Protein 1 Regulates the Postendocytic Sorting of Seven-Transmembrane-Spanning G Protein-Coupled Receptors

et al. 2010

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The largest superfamily of membrane proteins that translate extracellular signals into intracellular messages are the 7-transmembrane-spanning (7TM) G protein-coupled receptors (GPCR). One of the ways in which their activity is controlled is by the process of desensitization and endocytosis, whereby agonist-activated receptors are rapidly and often reversibly silenced through removal from the cell surface. Indeed, following endocytosis, individual receptors can be sorted differentially between recycling endosomes and lysosomes, which controls the reversibility of the silencing. Thus, endocytosis can either serve as a mechanism for receptor resensitization by delivering receptors back to the plasma membrane or facilitate receptor downregulation by serving as the first step towards targeting the receptors to lysosomes for degradation. The sorting of receptors to the lysosomal pathway can be facilitated by interaction with an array of accessory proteins. One of these proteins is the GPCR-associated sorting protein 1 (GASP-1), which specifically targets several 7TM-GPCR to the lysosomal pathway after endocytosis. Furthermore, GASP-1 was recently found to directly affect the signaling capacity of a 7TM-GPCR. Importantly, the in vivo relevance of GASP-1-dependent receptor sorting has also begun to be verified in animal models. Here, we summarize the recent advances in elucidating GASP-1-dependent receptor sorting functions and their potential implications in vivo.

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Section: Gasp-1: Regulator Of Signal Transduction?mentioning

confidence: 75%

Section: Gasp-1: Regulator Of Signal Transduction?mentioning

confidence: 99%

Section: Gasp-1: Regulator Of Signal Transduction?mentioning

confidence: 99%

Section: Postendocytic Sorting Of 7tm-gpcrsmentioning

confidence: 99%

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G Protein-Coupled Receptor-Associated Sorting Protein 1 Regulates the Postendocytic Sorting of Seven-Transmembrane-Spanning G Protein-Coupled Receptors

et al. 2010

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“…US28 constitutively activates multiple transcription factors, in- ]inositol according to methods described previously (28). Data are presented as means Ϯ SD from 2 experiments performed in triplicate; asterisks indicate significant difference between the responses with and without fractalkine (Student's t test; *, P Ͻ 0.05; **, P Ͻ 0.01; ***, P Ͻ 0.001).…”

Section: Fig 1 (A)mentioning

confidence: 99%

Identification of Common Mechanisms by Which Human and Mouse Cytomegalovirus Seven-Transmembrane Receptor Homologues Contribute to In Vivo Phenotypes in a Mouse Model

Farrell

Abraham

Cardin

et al. 2013

J Virol

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The mouse cytomegalovirus chemokine receptor homologue (CKR) M33 is required for salivary gland tropism and efficient reactivation from latency, phenotypes partially rescued by the human cytomegalovirus CKR US28. Herein, we demonstrate that complementation of salivary gland tropism is mediated predominantly by G protein-dependent signaling conserved with that of M33; in contrast, both G protein-dependent and -independent pathways contribute to the latency phenotypes. A novel M33-dependent replication phenotype in cultured bone marrow macrophages is also described.

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Gα13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced cell death in melanoma

et al. 2015

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US28, a constitutively active G-protein-coupled receptor encoded by the human cytomegalovirus, leads to mechanistically unknown programmed cell death. Here we show that expression of wild type US28 in human melanoma cells leads to apoptotic cell death via caspase 3 activation along with reduced cell proliferation. Reduced tumor growth upon US28 expression was observed in a xenograft mouse model. The signaling mute US28R129A showed a reduced anti-proliferative effect. On evaluating different G-proteins coupled to US28 for signal transduction, Gα13 was identified as the main G-protein executing the apoptotic effect. Silencing of Gα13 but not Gαq resulted in a substantial increase in cell survival. Over-expression of Gα13 but not Gαq and their GTPase deficient forms Gα13Q226L and GαqQ209L, respectively, confirmed the requirement of Gα13 for US28 mediated cell death. Increasing expression of Gα13 alone induced cell death underscoring its relay function for US28 mediated decreased cell viability. Further reduced expression of Gα13 in melanoma cell lines isolated from advanced lesions and melanoma tissue was observed. These findings identified Gα13 as crucial for US28 induced cell death, substantiating that the effect of US28 on cell fate depends on preferred G-protein binding.

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The G protein-coupled receptor associated sorting protein GASP-1 regulates the signaling and trafficking of the viral chemokine receptor US28

Cited by 7 publications

References 27 publications

G Protein-Coupled Receptor-Associated Sorting Protein 1 Regulates the Postendocytic Sorting of Seven-Transmembrane-Spanning G Protein-Coupled Receptors

G Protein-Coupled Receptor-Associated Sorting Protein 1 Regulates the Postendocytic Sorting of Seven-Transmembrane-Spanning G Protein-Coupled Receptors

Identification of Common Mechanisms by Which Human and Mouse Cytomegalovirus Seven-Transmembrane Receptor Homologues Contribute to In Vivo Phenotypes in a Mouse Model

Gα13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced cell death in melanoma

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