RECEPTOR BIOLOGY Receptor biology: Endophilin and the ß1-Adrenergic Receptor are Binding Partners

Abstract: The ß1 and ß2 subtypes of the ß-adrenergic receptor (ß-AR) both couple to the heterotrimeric protein Gs to activate adenyl cyclase, and like other G protein-coupled receptors, are then internalized from the cell surface into endosomes. It has been thought that the presence of a proline-rich region in the cytoplasmic tail of the ß1-AR could account for differences that the receptor subtypes exhibit in signaling and function. For example, ß1-AR couples less efficiently to the Gs protein. Tang et al. find further support of this idea by demonstrating that the proline region in ß1-AR binds to the SH3-domain of endophilin. The endopohilin family of proteins is known to regulate the formation and transport of synaptic vesicles in neurons. When ß1-AR and endophilin are overexpressed, the proteins interact in vivo, even in the absence of agonist stimulation. Overexpression of endophilin also increased agonist-induced internalization of ?1-AR, and decreased the receptor's Gs-coupling efficiency. The authors propose that interaction with the SH3 domain may alter ß1-AR's ability to stimulate Gs and may also direct the receptor to the cell's endocytic machinery.

Tang, Y., Hu, L.A., Miller, W.E., Ringstand, N., Hall, R.A., Pitcher, J.A., DeCamilli, P., and Lefkowitz, R.J. (1999) Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the ß1-adrenergic receptor. Proc. Natl. Acad. Sci. U.S.A. 96:12559-12564. [Abstract] [Full Text]