Premium
Interaction of Activator of G‐protein Signaling 3 (AGS3) and the signaling protein Dishevelled: Implications for the regulated distribution AGS3 within the cell and its functional diversity
Author(s) -
VURAL ALI,
LANIER STEPHEN
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb391
Subject(s) - microbiology and biotechnology , biology , cytosol , activator (genetics) , cytoplasm , endosome , phosphorylation , dishevelled , signal transduction , intracellular , receptor , biochemistry , frizzled , wnt signaling pathway , enzyme
Activator of G‐protein Signaling 3 (AGS3), a receptor independent activator of G‐protein signaling, consists of 7 tetratricopeptide repeats (TPR) upstream from 4 G‐protein regulatory motifs (GPR), each of which interact with GαGDP. AGS3 moves among multiple cellular compartments including cytosol, the cell cortex, the Golgi apparatus, the aggresomes and cellular puncta, with suggested oscillation between hydrophilic and hydrophobic domains. Such a regulated subcellular distribution is intimately related to the functional diversity of the protein, which remains mechanistically elusive. We recently reported that a mutation of a single threonine residue in the AGS3‐GPR domain alters the apparent phosphorylation status of the protein and results in the localization of AGS3‐T602A to punctate subcellular structures in contrast to the more diffuse, cytosolic distribution observed with WT AGS3. Moreover, these puncta are distinct from defined intracellular organelles or vesicles and their localization is regulated by interaction with AGS3 binding partners and potentially by the phosphorylation status of AGS3. In a search for proteins that exhibited a similar punctate distribution, we determined that the Dishevelled protein 2 (Dvl‐2) exhibits a punctate cellular distribution that is actually a “mirror” image of that observed with the AGS3‐T602A. However, co‐expression of AGS3‐T602A with Dvl‐2 indicated that the two proteins were localized to distinct punctate populations in the cell. In contrast AGS3‐WT, which typically has a non‐homogeneous, diffuse distribution in the cytosol, was actually redistributed to Dvl‐2 puncta upon co‐expression of the two proteins. The Dvl‐2 induced localization of WT AGS3 to puncta was reversed by coexpression of Giα3, which likely reflects the interaction of Giα3 with the AGS3 GPR domains. This series of observations suggest that the positioning of AGS3 as part of the Dvl‐2 puncta may be phosphorylation‐dependent and regulated by G‐proteins. In addition, these observations taken together, suggests a potential role for AGS3 in canonical and noncanonical WNT signaling pathways involving Dvl‐2. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .