A specific role of AGS3 in the surface expression of plasma membrane proteins.
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.
Groves
B
B
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106.
Gong
Q
Q
Xu
Z
Z
Huntsman
C
C
Nguyen
C
C
Li
D
D
Ma
D
D
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D034741:RNA, Small Interfering
D002352:Carrier Proteins; C525615:GPSM1 protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; C489457:KCNJ2 protein, human; D008565:Membrane Proteins; D024661:Potassium Channels, Inwardly Rectifying; D034741:RNA, Small Interfering