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- Title
Endocytosis of the Viral Chemokine Receptor US28 Does Not Require Beta-Arrestins But Is Dependent on the Clathrin-Mediated Pathway.
- Authors
Fraile-Ramos, Alberto; Kohout, Trudy A.; Waldhoer, Maria; Marsh, Mark
- Abstract
Arrestins bind phosphorylated G-protein coupled-receptors (GPCR) and inhibit agonist-induced signal transduction by uncoupling the receptors from their cognate G-proteins. β-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 β-arrestins in US28 trafficking, we used embryonic fibroblasts derived from β-arrestin knockout mice. In these cells, the internalization of transfected β2-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 μ2-adaptin subunit of the AP-2 adaptor complex. In cells transfected with μ2 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 β-arrestins .
- Subjects
ENDOCYTOSIS; CHEMOKINES; CELL receptors
- Publication
Traffic, 2003, Vol 4, Issue 4, p243
- ISSN
1398-9219
- Publication type
Article
- DOI
10.1034/j.1600-0854.2003.00079.x