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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zhang, Xin Mitchison, Timothy J. Wang, Wenchao Coughlin, Margaret L. Bedigian, Anne V. Eggert, Ulrike S. |
| Description | Author Affiliation: Zhang X ( Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.); |
| Abstract | Macromolecules enter cells by endocytosis and are sorted to different cellular destinations in early/sorting endosomes. The mechanism and regulation of sorting are poorly understood, although transitions between vesicular and tubular endosomes are important. We found that the antihypertensive drug Prazosin inhibits endocytic sorting by an off-target perturbation of the G protein-coupled receptor dopamine receptor D(3) (DRD3). Prazosin is also a potent cytokinesis inhibitor, likely as a consequence of its effects on endosomes. Prazosin stabilizes a normally transient interaction between DRD3 and the coatomer COPI, a complex involved in membrane transport, and shifts endosomal morphology entirely to tubules, disrupting cargo sorting. RNAi depletion of DRD3 alone also inhibits endocytic sorting, indicating a noncanonical role for a G protein-coupled receptor. Prazosin is a powerful tool for rapid and reversible perturbation of endocytic dynamics. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 31 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Adrenergic Alpha-1 Receptor Antagonists Pharmacology Coat Protein Complex I Metabolism Endocytosis Drug Effects Endosomes Prazosin Receptors, Dopamine D3 Biological Transport, Active Genetics HeLa Cells Protein Stability Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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