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Functional characterization of the alpha1D‐AR/syntrophin signaling complex
Author(s) -
Lyssand John Sverre,
DeFino Mia C,
Hertz Angie L,
Feller David B,
Tang Xiaobo,
Adams Marvin E,
Wacker Jennifer L,
Hague Chris
Publication year - 2008
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.22.1_supplement.726.7
Subject(s) - chemistry , microbiology and biotechnology , in vivo , biology , genetics
Previously, we reported the identification of syntrophins as novel accessory proteins for α 1D ‐adrenergic receptors (ARs). To characterize the functional importance of this interaction, we examined the role of syntrophins on α 1D ‐AR function in vitro and in vivo . Syntrophins increase α 1D ‐AR binding site density and functional coupling in HEK293 cells, with β 2 >β 1 >β 1 . To examine the importance of each domain in syntrophin to α 1D ‐AR function, an α 1D ‐AR/α 1 ‐syntrophin fusion construct was created with α 1 ‐ syntrophin tethered to the α 1D ‐AR C‐terminus. Using this technique, we determined the syntrophin unique domain is critical for α 1D ‐AR function. Mass spectrometry was next used to identify potential accessory proteins recruited by α 1 ‐syntrophin to the α 1D ‐AR signaling complex. In vivo , syntrophin KO mice have a 10% decrease in resting MAP and i.p. phenylephrine (PE) causes minor increases in MAP. Interestingly, PE effects are unaffected by the α 1D ‐AR antagonist BMY 7378, suggesting α 1D ‐AR stimulated increases in MAP are abrogated. From these studies, we conclude syntrophins are essential regulators of α 1D ‐AR function in vivo through regulation of the α 1D ‐AR protein signaling network.