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Characterization of the α 1D ‐Adrenergic Receptor Signalosome
Author(s) -
Lyssand John Sverre,
DeFino Mia C,
Tang Xiaobo,
Wacker Jennifer L,
Gardner Richard G,
Adams Marvin E,
Hague Chris
Publication year - 2010
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.24.1_supplement.771.5
Subject(s) - in vivo , microbiology and biotechnology , receptor , chemistry , in vitro , biophysics , biology , biochemistry , genetics
Previously, we reported the identification of syntrophins as novel accessory proteins for α 1D ‐adrenergic receptors (ARs). Syntrophins are members of the dystrophin complex, and act as scaffolds for anchoring membrane proteins to cytoskeletal proteins. To characterize the functional importance of this interaction, we examined how syntrophins contribute to α 1D ‐AR function in vitro and in vivo. In vitro , syntrophins increase α 1D ‐AR binding site density and functional coupling in HEK293 cells. In vivo, α‐ and β 2 ‐syntrophin double knock‐out mice have significantly diminished α 1D ‐AR functional responses in comparison to wild type mice. Taken together, these findings suggest that syntrophins play an essential role for α 1D ‐AR function in vivo , presumably by anchoring α 1D ‐ARs in the plasma membrane as a functional signalosome, and by recruiting necessary components into the signalosome. Next, we determined what proteins syntrophins recruit to the α 1D ‐AR signalosome, by performing tandem affinity purification (TAP)/mass spectrometry on α 1D ‐AR, α/β 1 /β 2 ‐syntrophin, and α‐dystrobrevin‐1/2. Our data revealed both previously identified and novel proteins recruited to the α 1D ‐AR/syntrophin signalosome. Current experiments are examining how these recruited proteins contribute to α 1D ‐AR function in vivo . Research was supported in part by PHS NRSA T32 GM07270 from NIGMS.