These authors contributed equally to this work.
The G-protein Coupled Receptor Associated Sorting Protein GASP-1 Regulates the Signalling and Trafficking of the Viral Chemokine Receptor US28
Article first published online: 22 FEB 2010
© 2010 John Wiley & Sons A/S
Volume 11, Issue 5, pages 660–674, May 2010
How to Cite
Tschische, P., Moser, E., Thompson, D., Vischer, H. F., Parzmair, G. P., Pommer, V., Platzer, W., Schwarzbraun, T., Schaider, H., Smit, M. J., Martini, L., Whistler, J. L. and Waldhoer, M. (2010), The G-protein Coupled Receptor Associated Sorting Protein GASP-1 Regulates the Signalling and Trafficking of the Viral Chemokine Receptor US28. Traffic, 11: 660–674. doi: 10.1111/j.1600-0854.2010.01045.x
- Issue published online: 13 APR 2010
- Article first published online: 22 FEB 2010
- Received 10 July 2009, Revised and accepted for publication 20 January 2010, published online 22 February 2010
- G-protein coupled receptor;
- post-endocytic sorting;
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.