A specific role of AGS3 in the surface expression of plasma membrane proteins
- Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106
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Communicated by Lily Y. Jan, University of California School of Medicine, San Francisco, CA, September 29, 2007 (received for review May 22, 2007)
Abstract
Activator of G protein signaling 3 (AGS3), originally identified in a functional screen for mammalian proteins that activate heterotrimeric G protein signaling, is known to be involved in drug-seeking behavior and is up-regulated during cocaine withdrawal in animal models. These observations indicate a potential role for AGS3 in the formation or maintenance of neural plasticity. We have found that the overexpression of AGS3 alters the surface-to-total ratios of a subset of heterologously expressed plasma membrane receptors and channels. Further analysis of the endocytic trafficking of one such protein by a biotin-based internalization assay suggests that overexpression of AGS3 moderately affects the internalization or recycling of surface proteins. Moreover, AGS3 overexpression and siRNA-mediated knockdown of AGS3 both result in the dispersal of two endogenously expressed trans-Golgi network (TGN)-associated cargo proteins without influencing those in the cis- or medial-Golgi compartments. Finally, adding a TGN-localization signal to a CD4-derived reporter renders the trafficking of fusion protein sensitive to AGS3. Taken together, our data support a model wherein AGS3 modulates the protein trafficking along the TGN/plasma membrane/endosome loop.
Footnotes
- *To whom correspondence should be addressed. E-mail: ma{at}lifesci.ucsb.edu
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Author contributions: B.G., Q.G., and Z.X. contributed equally to this work; D.M. designed research; B.G., Q.G., Z.X., C.H., C.N., D.L., and D.M. performed research; B.G., Q.G., Z.X., and D.M. analyzed data; and B.G. and D.M. wrote the paper.
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The authors declare no conflict of interest.
- Abbreviations:
- AG53,
- activator of G protein signaling 3;
- ER,
- endoplasmic reticulum;
- GPCR,
- G protein-coupled receptor;
- TGN,
- trans-Golgi network.
- © 2007 by The National Academy of Sciences of the USA
