Enhancement of the Recycling and Activation of beta-Adrenergic Receptor by Rab4 GTPase in Cardiac Myocytes.
We investigate the role of Rab4, a Ras-like small GTPase coordinating protein transport from the endosome to the plasma membrane, on the recycling and activation of endogenous beta-adrenergic receptor (beta-AR) in HL-1 cardiac myocytes in vitro and transgenic mouse hearts in vivo. beta(1)-AR, the predominant subtype of beta-AR in HL-1 cardiac myocytes, was internalized after stimulation with isoproterenol (ISO) and fully recycled at 4 h upon ISO removal. Transient expression of Rab4 markedly facilitated recycling of internalized beta-AR to the cell surface and enhanced beta-AR signaling as measured by ISO-stimulated cAMP production. Transgenic overexpression of Rab4 in the mouse myocardium significantly increased the number of beta-AR in the plasma membrane and augmented cAMP production at the basal level and in response to ISO stimulation. Rab4 overexpression induced concentric cardiac hypertrophy with a moderate increase in ventricle/body weight ratio and posterior wall thickness and a selective up-regulation of the beta-myosin heavy chain gene. These data provide the first evidence indicating that Rab4 is a rate-limiting factor for the recycling of endogenous beta-AR and augmentation of Rab4- mediated traffic enhances beta-AR function in cardiac myocytes.[1]References
- Enhancement of the Recycling and Activation of beta-Adrenergic Receptor by Rab4 GTPase in Cardiac Myocytes. Filipeanu, C.M., Zhou, F., Lam, M.L., Kerut, K.E., Claycomb, W.C., Wu, G. J. Biol. Chem. (2006) [Pubmed]
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