Caveolin, a protein component of caveolae membrane coats

doi:10.1016/0092-8674(92)90143-Z

Cell

Volume 68, Issue 4, 21 February 1992, Pages 673-682

https://doi.org/10.1016/0092-8674(92)90143-Z Get rights and content

Abstract

Caveolae have been implicated in the transcytosis of macromolecules across endothelial cells and in the receptor-mediated uptake of 5-methyltetrahydrofolate. Structural studies indicate that caveolae are decorated on their cytoplasmic surface by a unique array of filaments or strands that form striated coatings. To understand how these nonclathrin-coated pits function, we performed structural analysis of the striated coat and searched for the molecular component(s) of the coat material. The coat cannot be removed by washing with high salt; however, exposure of membranes to cholesterol-binding drugs caused invaginated caveolae to flatten and the striated coat to disassemble. Antibodies directed against a 22 kd substrate for v-src tyrosine kinase in virus-transformed chick embryo fibroblasts decorated the filaments, suggesting that this molecule is a component of the coat. We have named the molecule caveolin. Caveolae represent a third type of coated membrane specialization that is involved in molecular transport.

References (50)

M.M. Bradford
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
Anal. Biochem.
(1976)
M.S. Bretscher et al.
Membrane-associated vesicles in fibroblasts
J. Ultrastruct. Res.
(1977)
M. Bundgaard et al.
The three-dimensional organization of plasmalemmal vesicular profiles in the endothelium of rat heart capillaries
Microvasc. Res.
(1983)
G. Clough
Relationship between microvascular permeability and ultrastructure
Prog. Biophys. Molec. Biol.
(1991)
M.S. Forbes et al.
Caveolar systems and sarcoplasmic reticulum in coronary smooth muscle cells of the mouse
J. Ultrastruct. Res.
(1979)
J.R. Glenney
Tyrosine phosphorylation of a 22-kd protein is correlated with transformation by Rous sarcoma virus
J. Biol. Chem.
(1989)
J.L. Goldstein et al.
Receptor-mediated endocytosis of LDL in cultured cells
Meth. Enzymol.
(1983)
B.A. Kamen et al.
Delivery of folates to the cytoplasm of MA104 cells is mediated by a surface membrane receptor that recycles
J. Biol. Chem.
(1988)
M.P. Kamps et al.
Rous sarcoma virus transforming protein lacking myristic acid phosphorylates known polypeptide substrates without inducing transformation
Cell
(1986)
D.T. Mahaffey et al.
Clathrin-coated pits contain an integral membrane protein that binds the AP-2 subunit with high affinity
J. Biol. Chem.
(1990)

L. Orci et al.

Dissection of a single round of vesicular transport: sequential intermediates for intercisternal movement in the Golgi stack

Cell

(1989)

R.G.W. Anderson

Molecular motors that shape endocytic membrane

M. Bundgaard

Vesicular transport in capillary endothelium: does it occur?

M. Bundgaard et al.

Endothelial plasmalemmal vesicles as elements in a system of branching invaginations from the cell surface

D.S. Crow et al.

Phosphorylation of connexin43 gap junction protein in uninfected and Rous sarcoma virus-transfected mammalian fibroblasts

Mol. Cell. Biol.

(1990)

L. Ghitescu et al.

Specific binding sites for albumin restricted to plasmalemmal vesicles of continuous capillary endothelium: receptor-mediated transcytosis

J. Cell Biol.

(1986)

J.R. Glenney et al.

Novel tyrosine kinase substrates from Rous sarcoma virus transformed cells are present in the membrane skeleton

J. Cell Biol.

(1989)

J. Heuser et al.

Three-dimensional visualization of coated vesicle formation in fibroblasts

J. Cell Biol.

(1980)

T. Izumi et al.

The cytoplasmic surface structure of uncoated vesicles in various tissues of rat as revealed by quick-freeze, deep-etching replicas

J. Electron Microsc.

(1989)

B.A. Kamen et al.

Receptor-mediated folate accumulation is regulated by the cellular folate content

B.A. Kamen et al.

Regulation of the cytoplasmic accumulation of 5-methyltetrahy-drofolate in MA 104 cells is independent of folate receptor regulation

J. Clin. Invest.

(1989)

B.A. Kamen et al.

The folate receptor works in tandem with a probenecid-sensitive anion carrier

J. Clin. Invest.

(1991)

S.W. Lacey et al.

cDNA for the folate binding protein correctly predicts anchoring to the membrane by glycosylphosphatidylinositol

J. Clin. Invest.

(1989)

U.K. Laemmli

Cleavage of structural proteins during the assembly of the head of bacteriophage T4

Nature

(1970)

J.M. Larkin et al.

Potassium-dependent assembly of coated pits: new coated pits form as planar clathrin lattices

J. Cell Biol.

(1986)

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The expression of CAV1 in microglia/macrophages (Iba1+ cells) was elevated and reached the peak at 24 h after ICH. CAV1 knockdown ameliorated ICH-induced neurological deficits, while CAV1 overexpression significantly worsened neurological dysfunction of ICH rats. CAV1 knockdown attenuated cellular apoptosis and promoted neuronal survival in brain tissues of ICH rats, while the ICH rats with CAV1 overexpression presented more cellular apoptosis and neuronal loss. Meanwhile, CAV1 knockdown inhibited the microglia activation and neuroinflammatory response, while CAV1 overexpression abolished these effects and aggravated neuroinflammation in brain tissues of ICH rats. Additionally, by inducing to CAV1 knockdown in BV2 cells in an in vitro model of ICH, the levels of p-C-Src, CAV-1, p-CAV-1, and p-IKK-β in cytoplasm and the level of NF-κB p65 in nucleus of BV2 cells were significantly decreased, while they were increased by inducing to CAV1 overexpression.
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Cell

ArticleCaveolin, a protein component of caveolae membrane coats

Abstract

Anal. Biochem.

J. Ultrastruct. Res.

Microvasc. Res.

Prog. Biophys. Molec. Biol.

J. Ultrastruct. Res.

J. Biol. Chem.

Meth. Enzymol.

J. Biol. Chem.

Cell

J. Biol. Chem.

Cell

Molecular motors that shape endocytic membrane

Vesicular transport in capillary endothelium: does it occur?

Endothelial plasmalemmal vesicles as elements in a system of branching invaginations from the cell surface

Phosphorylation of connexin43 gap junction protein in uninfected and Rous sarcoma virus-transfected mammalian fibroblasts

Mol. Cell. Biol.

Specific binding sites for albumin restricted to plasmalemmal vesicles of continuous capillary endothelium: receptor-mediated transcytosis

J. Cell Biol.

Novel tyrosine kinase substrates from Rous sarcoma virus transformed cells are present in the membrane skeleton

J. Cell Biol.

Three-dimensional visualization of coated vesicle formation in fibroblasts

J. Cell Biol.

The cytoplasmic surface structure of uncoated vesicles in various tissues of rat as revealed by quick-freeze, deep-etching replicas

J. Electron Microsc.

Receptor-mediated folate accumulation is regulated by the cellular folate content

Regulation of the cytoplasmic accumulation of 5-methyltetrahy-drofolate in MA 104 cells is independent of folate receptor regulation

J. Clin. Invest.

The folate receptor works in tandem with a probenecid-sensitive anion carrier

J. Clin. Invest.

cDNA for the folate binding protein correctly predicts anchoring to the membrane by glycosylphosphatidylinositol

J. Clin. Invest.

Cleavage of structural proteins during the assembly of the head of bacteriophage T4

Nature

Potassium-dependent assembly of coated pits: new coated pits form as planar clathrin lattices

J. Cell Biol.

Article
Caveolin, a protein component of caveolae membrane coats