Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Navigation/Suche
- Forscher*innen
- Institutionen
- Projekte
- Publikationen
- Partner
- Geldgeber
- Ausstattung
- Knowhow
- Forschungsfelder
"Köpfe" der aktuellen Meldungen:
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Tschische, P; Moser, E; Thompson, D; Vischer, HF; Parzmair, GP; Pommer, V; Platzer, W; Schwarzbraun, T; Schaider, H; Smit, MJ; Martini, L; Whistler, JL; Waldhoer, M.
The G-protein coupled receptor associated sorting protein GASP-1 regulates the signalling and trafficking of the viral chemokine receptor US28.
Traffic. 2010; 11(5):660-674
Doi: 10.1111/j.1600-0854.2010.1045.x
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Moser Elisabeth
- Tschische Pia
- Waldhoer Maria
- Co-Autor*innen der Med Uni Graz
- Parzmair Gerald Peter
- Platzer Wolfgang
- Pommer Veronika
- Schaider Helmut
- Schwarzbraun Thomas
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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 Galphaq/PLC/inositol phosphate (IP) accumulation as well as the activation of the transcription factors Nuclear Factor-kappaB (NF-kappaB) 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Chemokines - metabolism
- Cyclic AMP Response Element-Binding Protein - metabolism
- Cytomegalovirus - genetics Cytomegalovirus - metabolism
- Endocytosis -
- Humans -
- Inositol Phosphates - metabolism
- Ligands -
- NF-kappa B - metabolism
- Proteins - metabolism
- Receptors, Chemokine - genetics Receptors, Chemokine - metabolism Receptors, Chemokine - physiology
- Receptors, G-Protein-Coupled - metabolism Receptors, G-Protein-Coupled - physiology
- Signal Transduction -
- Type C Phospholipases - metabolism
- Find related publications in this database (Keywords)
- chemokine
- cytomegalovirus
- GASP-1
- G-protein coupled receptor
- post-endocytic sorting
- signalling
- US28