Regulation of transport of the angiotensin AT2 receptor by a novel membrane-associated Golgi protein.
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.


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.


CONCLUSIONS
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.
Wruck
Christoph J
CJ
Institute of Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Germany. thomas.unger@charite.de
Funke-Kaiser
Heiko
H
Pufe
Thomas
T
Kusserow
Heike
H
Menk
Mario
M
Schefe
Jan H
JH
Kruse
Marie L
ML
Stoll
Monika
M
Unger
Thomas
T
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000737:chemistry; D006056:Golgi Apparatus / Q000737:chemistry*; D008565:Membrane Proteins / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology; D016716:PC12 Cells / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics; D021382:Protein Sorting Signals / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D051381:Rats; D044139:Receptor, Angiotensin, Type 2 / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D002352:Carrier Proteins; D025521:Tumor Suppressor Proteins
D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D010455:Peptides; D020033:Protein Isoforms; D021382:Protein Sorting Signals; D044139:Receptor, Angiotensin, Type 2; C488664:Mtus1 protein, mouse; D002352:Carrier Proteins; D025521:Tumor Suppressor Proteins