Enhancement of the recycling and activation of β-adrenergic receptor by Rab4 GTPase in cardiac myocytes

Catalin M. Filipeanu, Fuguo Zhou, May L. Lam, Kenneth E. Kerut, William C. Claycomb, Guangyu Wu

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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 β-adrenergic receptor (β-AR) in HL-1 cardiac myocytes in vitro and transgenic mouse hearts in vivo. β1-AR, the predominant subtype of β-AR in HL-1 cardiac myocytes, was internalized after stimulation with iso-proterenol (ISO) and fully recycled at 4 h 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 up-regulation 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.

Original languageEnglish (US)
Pages (from-to)11097-11103
Number of pages7
JournalJournal of Biological Chemistry
Volume281
Issue number16
DOIs
StatePublished - Apr 21 2006
Externally publishedYes

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GTP Phosphohydrolases
Recycling
Cardiac Myocytes
Adrenergic Receptors
Chemical activation
Cell membranes
Cell Membrane
Monomeric GTP-Binding Proteins
Myosin Heavy Chains
Endosomes
Cardiomegaly
Protein Transport
Transgenic Mice
Myocardium
Up-Regulation
Genes
Body Weight
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Enhancement of the recycling and activation of β-adrenergic receptor by Rab4 GTPase in cardiac myocytes. / Filipeanu, Catalin M.; Zhou, Fuguo; Lam, May L.; Kerut, Kenneth E.; Claycomb, William C.; Wu, Guangyu.

In: Journal of Biological Chemistry, Vol. 281, No. 16, 21.04.2006, p. 11097-11103.

Research output: Contribution to journalArticle

Filipeanu, Catalin M. ; Zhou, Fuguo ; Lam, May L. ; Kerut, Kenneth E. ; Claycomb, William C. ; Wu, Guangyu. / Enhancement of the recycling and activation of β-adrenergic receptor by Rab4 GTPase in cardiac myocytes. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 16. pp. 11097-11103.
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