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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:57.)
© 2005 American Heart Association, Inc.

Vascular Biology

Regulation of Transport of the Angiotensin AT2 Receptor by a Novel Membrane-Associated Golgi Protein

Christoph J. Wruck; Heiko Funke-Kaiser; Thomas Pufe; Heike Kusserow; Mario Menk; Jan H. Schefe; Marie L. Kruse; Monika Stoll; Thomas Unger

From the Institute of Pharmacology (C.J.W.) and the First Department of Medicine (M.L.K.), University Hospital Schleswig-Holstein, Campus Kiel; the Institute of Anatomy (T.P.), University of Kiel; the Center for Cardiovascular Research/Institute of Pharmacology and Toxicology (H.F.-K., H.K., M.M., J.H.S., T.U.), Charité–University Medicine Berlin; and the Institute for Arteriosclerosis Research at the University of Muenster (M.S.), Germany.

Correspondence to Thomas Unger, MD, Center for Cardiovascular Research/Institute of Pharmacology and Toxicology, Charité–University Medicine Berlin, Hessische Str. 3-4, 10115 Berlin, Germany. E-mail thomas.unger{at}charite.de

Objective— Synthesis and maturation of G protein–coupled receptors are complex events that require an intricate combination of processes including protein folding, posttranslational modifications, and transport through distinct cellular compartments. Little is known concerning the regulation of G protein–coupled receptor transport from the endoplasmic reticulum to the cell surface.

Methods and Results— Here we show that the cytoplasmatic carboxy-terminal of the angiotensin AT2 receptor (AT2R) acts independently as an endoplasmic reticulum–export signal. Using a yeast two-hybrid system, we identified a Golgi membrane–associated protein termed ATBP50 (for AT2R binding protein of 50 kDa) that binds to this motif. We also cloned ATBP60 and ATBP135 encoded by the same gene as ATBP50 that mapped to chromosomes 8p21.3. Downregulation of ATBP50 using siRNA leads to retention of AT2R in inner compartments, reduced cell surface expression, and decreased antiproliferative effects of the receptor.

Conclusion— Our results indicate that ATBP50 regulates the transport of the AT2R to cell membrane by binding to a specific motif within its cytoplasmic carboxy-terminal and thereby enabling the antiproliferative effects of the receptor.

We identified a Golgi membrane–associated protein termed ATBP50 that binds to the cytoplasmatic terminus of the angiotensin AT2 receptor. We also cloned ATBP60 and ATBP135 encoded by the same gene. Downregulation of ATBP50 leads to retention of AT2R in inner compartments, reduced cell surface expression, and decreased antiproliferative effects of AT2R.

Key Words: AT2 receptor • ATBP50 • receptor transport • Golgi proteins • ERK1/2

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Beyond the G Protein: The Saga of the Type 2 Angiotensin II Receptor

E.J. Landon and T. Inagami
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