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- Title
The G-protein Coupled Receptor Associated Sorting Protein GASP-1 Regulates the Signalling and Trafficking of the Viral Chemokine Receptor US28.
- Authors
Tschische, Pia; Moser, Elisabeth; Thompson, Dawn; Vischer, Henry F.; Parzmair, Gerald P.; Pommer, Veronika; Platzer, Wolfgang; Schwarzbraun, Thomas; Schaider, Helmut; Smit, Martine J.; Martini, Lene; Whistler, Jennifer L.; Waldhoer, Maria
- Abstract
Human cytomegalovirus (HCMV) encodes the seven transmembrane (7TM)/G-protein coupled receptor (GPCR) US28, which signals and endocytoses in a constitutive, ligand-independent manner. Here we show that, following endocytosis, US28 is targeted to the lysosomes for degradation as a consequence of its interaction with the GPCR-associated sorting protein-1 (GASP-1). We find that GASP-1 binds to US28 in vitro and that disruption of the GASP-1/US28 interaction by either (i) overexpression of dominant negative cGASP-1 or by (ii) shRNA knock-down of endogenous GASP-1 is sufficient to inhibit the lysosomal targeting of US28 and slow its post-endocytic degradation. Furthermore, we found that GASP-1 affects US28-mediated signalling. The knock-down of endogenous GASP-1 impairs the US28-mediated Gαq/PLC/inositol phosphate (IP) accumulation as well as the activation of the transcription factors Nuclear Factor–κB (NF-κB) and cyclic AMP responsive element binding protein (CREB). Overexpression of GASP-1 enhances both IP accumulation and transcription factor activity. Thus, GASP-1 is an important cellular determinant that not only regulates the post-endocytic trafficking of US28, but also regulates the signalling capacities of US28.
- Subjects
G proteins; TRANSCRIPTION factors; ENDOCYTOSIS; CELL physiology; CHEMOKINES
- Publication
Traffic, 2010, Vol 11, Issue 5, p660
- ISSN
1398-9219
- Publication type
Article
- DOI
10.1111/j.1600-0854.2010.01045.x