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Enhancement of the recycling and activation of β‐adrenergic receptor by Rab4 GTPase in cardiac myocytes
Author(s) -
Filipeanu Catalin,
Zhou Fuguo,
Lam May L,
Claycomb William C,
Wu Guangyu
Publication year - 2006
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.20.4.a257-a
Subject(s) - myocyte , medicine , stimulation , endocrinology , microbiology and biotechnology , receptor , ventricle , downregulation and upregulation , endogeny , biology , chemistry , gene , biochemistry
We investigated the role of Rab4, a Ras‐like small GTPase which coordinates protein transport specifically from the endosome to the plasma membrane, in the recycling and activation of endogenous β‐adrenergic receptor (β‐AR) in HL‐1 cardiac myocytes in vitro and transgenic mouse hearts in vivo. β 1 ‐AR, the predominant subtype of β‐AR in HL‐1 myocytes, is internalized after stimulation with isoproterenol (ISO) and fully recycled at 4 hrs upon ISO removal. Transient expression of Rab4 markedly facilitated recycling of internalized β‐AR to the cell surface and enhanced β‐AR signaling as measured by ISO‐stimulated cAMP production. Transgenic overexpression of Rab4 in the mouse myocardium significantly increased the number of β‐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 upregulation of the β‐myosin heavy chain gene. These data provide the first evidence indicating that Rab4 is a rate‐limiting factor for the recycling of endogenous β‐AR and augmentation of Rab4‐mediated traffic enhances β‐AR function in cardiac myocytes (P20RR018766).