Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Fraile-Ramos, A; Kohout, TA; Waldhoer, M; Marsh, M.
Endocytosis of the viral chemokine receptor US28 does not require beta-arrestins but is dependent on the clathrin-mediated pathway.
TRAFFIC 2003 4: 243-253.
Doi: 10.1034/j.1600-0854.2003.00079.x
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Waldhoer Maria
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Arrestins bind phosphorylated G-protein coupled-receptors (GPCR) and inhibit agonist-induced signal transduction by uncoupling the receptors from their cognate G-proteins. beta-arrestins also act as adaptors that target GPCR to endocytic clathrin-coated vesicles. Unlike cellular GPCRs, the human cytomegalovirus GPCRs and chemokine receptor, US28, shows constitutive signal transduction activity and undergoes constitutive endocytosis. To determine the role of beta-arrestins in US28 trafficking, we used embryonic fibroblasts derived from beta-arrestin knockout mice. In these cells, the internalization of transfected beta2-adrenergic receptor and of the cellular chemokine receptor CCR5 was impaired. By contrast, US28 distribution was unaffected, and US28-mediated RANTES internalization was similar in normal and knockout cell lines. To investigate whether a clathrin-mediated pathway is involved in US28 endocytosis, we developed small interfering RNA against the micro2-adaptin subunit of the AP-2 adaptor complex. In cells transfected with micro2 small interfering RNA transferrin endocytosis was severely inhibited. Antibody-feeding experiments and biochemical analysis showed that US28 internalization was also inhibited. Together, these data indicate that US28 endocytosis occurs via a clathrin-mediated mechanism but is independent of beta-arrestins.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Arrestins - genetics
- Base Sequence - genetics
- Clathrin - metabolism
- DNA Primers - metabolism
- Endocytosis - metabolism
- GTP-Binding Proteins - metabolism
- Mice - metabolism
- Mice, Knockout - metabolism
- Microscopy, Fluorescence - metabolism
- RNA, Small Interfering - metabolism
- Receptors, Cell Surface - metabolism
- Receptors, Chemokine - metabolism
- Research Support, Non-U.S. Gov't - metabolism
- Viral Proteins - metabolism
- Find related publications in this database (Keywords)
- beta-arrestin
- chemokine receptor
- endocytosis
- HCMV
- siRNA
- US28