Caveolin interacts with the angiotensin II type 1 receptor during exocytic transport but not at the plasma membrane

被引:106
作者
Wyse, BD
Prior, IA
Qian, HW
Morrow, IC
Nixon, S
Muncke, C
Kurzchalia, TV
Thomas, WG
Parton, RG
Hancock, JF [1 ]
机构
[1] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia
[2] Univ Queensland, Dept Mol & Cellular Pathol, Brisbane, Qld 4072, Australia
[3] Univ Queensland, Ctr Microscopy & Microanal, Brisbane, Qld 4072, Australia
[4] Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia
[5] Baker Heart Res Inst, Melbourne, Vic 3004, Australia
[6] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany
关键词
D O I
10.1074/jbc.M212892200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mechanisms involved in angiotensin II type 1 receptor (AT(1)-R) trafficking and membrane localization are largely unknown. In this study, we examined the role of caveolin in these processes. Electron microscopy of plasma membrane sheets shows that the AT(1)-R is not concentrated in caveolae but is clustered in cholesterol-independent microdomains; upon activation, it partially redistributes to lipid rafts. Despite the lack of AT(1)-R in caveolae, AT(1)-R. caveolin complexes are readily detectable in cells co-expressing both proteins. This interaction requires an intact caveolin scaffolding domain because mutant caveolins that lack a functional caveolin scaffolding domain do not interact with AT(1)-R. Expression of an N-terminally truncated caveolin-3, CavDGV, that localizes to lipid bodies, or a point mutant, Cav3-P104L, that accumulates in the Golgi mislocalizes AT(1)-R to lipid bodies and Golgi, respectively. Mislocalization results in aberrant maturation and surface expression of AT(1)-R, effects that are not reversed by supplementing cells with cholesterol. Similarly mutation of aromatic residues in the caveolin-binding site abrogates AT(1)-R cell surface expression. In cells lacking caveolin-1 or caveolin-3, AT(1)-R does not traffic to the cell surface unless caveolin is ectopically expressed. This observation is recapitulated in caveolin-1 null mice that have a 55% reduction in renal AT(1)-R levels compared with controls. Taken together our results indicate that a direct interaction with caveolin is required to traffic the AT(1)-R through the exocytic pathway, but this does not result in AT(1)-R sequestration in caveolae. Caveolin therefore acts as a molecular chaperone rather than a plasma membrane scaffold for AT(1)-R.
引用
收藏
页码:23738 / 23746
页数:9
相关论文
共 65 条
[1]   POTOCYTOSIS - SEQUESTRATION AND TRANSPORT OF SMALL MOLECULES BY CAVEOLAE [J].
ANDERSON, RGW ;
KAMEN, BA ;
ROTHBERG, KG ;
LACEY, SW .
SCIENCE, 1992, 255 (5043) :410-411
[2]   H-ras but not K-ras traffics to the plasma membrane through the exocytic pathway [J].
Apolloni, A ;
Prior, IA ;
Lindsay, M ;
Parton, RG ;
Hancock, JF .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (07) :2475-2487
[3]   Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease [J].
Betz, RC ;
Schoser, BGH ;
Kasper, D ;
Ricker, K ;
Ramírez, A ;
Stein, V ;
Torbergsen, T ;
Lee, YA ;
Nöthen, MM ;
Wienker, TF ;
Malin, JP ;
Propping, P ;
Reis, A ;
Mortier, W ;
Jentsch, TJ ;
Vorgerd, M ;
Kubisch, C .
NATURE GENETICS, 2001, 28 (03) :218-219
[4]   Hsp90 and caveolin are key targets for the proangiogenic nitric oxide-mediated effects of statins [J].
Brouet, A ;
Sonveaux, P ;
Dessy, C ;
Moniotte, S ;
Balligand, JL ;
Feron, O .
CIRCULATION RESEARCH, 2001, 89 (10) :866-873
[5]   Functions of lipid rafts in biological membranes [J].
Brown, DA ;
London, E .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 1998, 14 :111-136
[6]   Inhibition of lipid raft-dependent signaling by a dystrophy-associated mutant of caveolin-3 [J].
Carozzi, AJ ;
Roy, S ;
Morrow, IC ;
Pol, A ;
Wyse, B ;
Clyde-Smith, J ;
Prior, IA ;
Nixon, SJ ;
Hancock, JF ;
Parton, RG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (20) :17944-17949
[7]   Interaction of a receptor tyrosine kinase, EGF-R, with caveolins - Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities [J].
Couet, J ;
Sargiacomo, M ;
Lisanti, MP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (48) :30429-30438
[8]   Identification of peptide and protein ligands for the caveolin-scaffolding domain - Implications for the interaction of caveolin with caveolae-associated proteins [J].
Couet, J ;
Li, SW ;
Okamoto, T ;
Ikezu, T ;
Lisanti, MP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (10) :6525-6533
[9]   Mammalian prenylcysteine carboxyl methyltransferase is in the endoplasmic reticulum [J].
Dai, Q ;
Choy, E ;
Chiu, V ;
Romano, J ;
Slivka, SR ;
Steitz, SA ;
Michaelis, S ;
Philips, MR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (24) :15030-15034
[10]   Angiotensin receptors: distribution, signalling and function [J].
Dinh, DT ;
Frauman, AG ;
Johnston, CI ;
Fabiani, ME .
CLINICAL SCIENCE, 2001, 100 (05) :481-492