Mechanisms and functions of AT1 angiotensin receptor internalization

被引:93
作者
Hunyady, L
Catt, KJ
Clark, AJL
Gáborik, Z
机构
[1] Semmelweis Univ, Fac Med, Dept Physiol, H-1444 Budapest, Hungary
[2] NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA
[3] St Bartholomews Hosp, Dept Endocrinol, London, England
[4] St Bartholomews Hosp, Dept Chem Endocrinol, London, England
基金
英国惠康基金;
关键词
endocytosis; phosphorylation; dynamin; beta-arrestin; G protein-coupled receptor; Ca2+-mobilizing hormone;
D O I
10.1016/S0167-0115(00)00137-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The type I (AT(1)) angiotensin receptor, which mediates the known physiological and pharmacological actions of angiotensin II, activates numerous intracellular signaling pathways and undergoes rapid internalization upon agonist binding. Morphological and biochemical studies have shown that agonist-induced endocytosis of the AT(1) receptor occurs via clathrin-coated pits, and is dependent on two regions in the cytoplasmic tail of the receptor. However, it is independent of G protein activation and signaling, and does not require the conserved NPXXY motif in the seventh transmembrane helix. The dependence of internalization of the AT(1) receptor on a cytoplasmic serine-threonine-rich region that is phosphorylated during agonist stimulation suggests that endocytosis is regulated by phosphorylation of the AT(1) receptor tail. beta-Arrestins have been implicated in the desensitization and endocytosis of several G protein-coupled receptors, but the exact nature of the adaptor protein required for association of the AT(1) receptor with clathrin-coated pits, and the role of dynamin in the internalization process, are still controversial. There is increasing evidence for a role of internalization in sustained signal generation from the AT(1) receptor. Several aspects of the mechanisms and specific function of AT(1) receptor internalization, including its precise mode and route of endocytosis, and the potential roles of cytoplasmic and nuclear receptors, remain to be elucidated. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:29 / 44
页数:16
相关论文
共 171 条
[21]   ANGIOTENSIN-II-BINDING SITES ON HEPATOCYTE NUCLEI [J].
BOOZ, GW ;
CONRAD, KM ;
HESS, AL ;
SINGER, HA ;
BAKER, KM .
ENDOCRINOLOGY, 1992, 130 (06) :3641-3649
[22]   Endocytosis: How dynamin sets vesicles PHree! [J].
Bottomley, MJ ;
Lo Surdo, P ;
Driscoll, PC .
CURRENT BIOLOGY, 1999, 9 (08) :R301-R304
[23]   SHORT-TERM DESENSITIZATION OF THE ANGIOTENSIN-II RECEPTOR OF BOVINE ADRENAL GLOMERULOSA CELLS CORRESPONDS TO A SHIFT FROM A HIGH TO A LOW-AFFINITY STATE [J].
BOULAY, G ;
CHRETIEN, L ;
RICHARD, DE ;
GUILLEMETTE, G .
ENDOCRINOLOGY, 1994, 135 (05) :2130-2136
[24]  
Briand SI, 1999, J CELL BIOCHEM, V75, P587, DOI 10.1002/(SICI)1097-4644(19991215)75:4<587::AID-JCB5>3.0.CO
[25]  
2-Q
[26]   Desensitization of G-protein-coupled receptors in the cardiovascular system [J].
Bünemann, M ;
Lee, KB ;
Pals-Rylaarsdam, R ;
Roseberry, AG ;
Hosey, MM .
ANNUAL REVIEW OF PHYSIOLOGY, 1999, 61 :169-192
[27]   Regulated endocytosis of G-protein-coupled receptors by a biochemically and functionally distinct subpopulation of clathrin-coated pits [J].
Cao, TT ;
Mays, RW ;
von Zastrow, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (38) :24592-24602
[28]   Dynamin-dependent endocytosis of ionotropic glutamate receptors [J].
Carroll, RC ;
Beattie, EC ;
Xia, HH ;
Lüscher, C ;
Altschuler, Y ;
Nicoli, RA ;
Malenka, RC ;
von Zastrow, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (24) :14112-14117
[29]   ROLE OF CARBOXYL TAIL OF THE RAT ANGIOTENSIN-II TYPE 1A RECEPTOR IN AGONIST-INDUCED INTERNALIZATION OF THE RECEPTOR [J].
CHAKI, S ;
GUO, DF ;
YAMANO, Y ;
OHYAMA, K ;
TANI, M ;
MIZUKOSHI, M ;
SHIRAI, H ;
INAGAMI, T .
KIDNEY INTERNATIONAL, 1994, 46 (06) :1492-1495
[30]   Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis [J].
Chen, H ;
Fre, S ;
Slepnev, VI ;
Capua, MR ;
Takei, K ;
Butler, MH ;
Di Fiore, PP ;
De Camilli, P .
NATURE, 1998, 394 (6695) :793-797