Rapid Recycling of β2‐Adrenergic Receptors is Dependent on the Actin Cytoskeleton and Myosin Vb
Open Access
- 10 October 2008
- Vol. 9 (11) , 1958-1971
- https://doi.org/10.1111/j.1600-0854.2008.00813.x
Abstract
For the β2‐adrenergic receptor (β2AR), published evidence suggests that an intact actin cytoskeleton is required for the endocytosis of receptors and their proper sorting to the rapid recycling pathway. We have characterized the role of the actin cytoskeleton in the regulation of β2AR trafficking in human embryonic kidney 293 (HEK293) cells using two distinct actin filament disrupting compounds, cytochalasin D and latrunculin B (LB). In cells pretreated with either drug, β2AR internalization into transferrin‐positive vesicles was not altered but both agents significantly decreased the rate at which β2ARs recycled to the cell surface. In LB‐treated cells, nonrecycled β2ARs were localized to early embryonic antigen 1‐positive endosomes and also accumulated in the recycling endosome (RE), but only a small fraction of receptors localized to LAMP‐positive late endosomes and lysosomes. Treatment with LB also markedly enhanced the inhibitory effect of rab11 overexpression on receptor recycling. Dissociating receptors from actin by expression of the myosin Vb tail fragment resulted in missorting of β2ARs to the RE, while the expression of various CART fragments or the depletion of actinin‐4 had no detectable effect on β2AR sorting. These results indicate that the actin cytoskeleton is required for the efficient recycling of β2ARs, a process that likely is dependent on myosin Vb.Keywords
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