共 65 条
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