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PMID:15657086

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Citation

Nohe, A, Keating, E, Underhill, TM, Knaus, P and Petersen, NO (2005) Dynamics and interaction of caveolin-1 isoforms with BMP-receptors. J. Cell. Sci. 118:643-50

Abstract

Caveolae are small invaginations of the cell membrane that are thought to play a role in important physiological functions such as cell surface signaling, endocytosis and intracellular cholesterol transport. Caveolin-1 is a key protein in these domains and contributes to the organization of cholesterol and saturated lipids within these vesicular invaginations of the plasma membrane. Caveolae are thought to be involved in the signaling of tyrosine kinase receptors and serine threonine receptors. In this article we focus on the involvement of caveolae in the signal transduction of bone morphogenetic proteins (BMPs). BMPs play important roles during embryonic development and especially in chondrogenesis, osteogenesis, neurogenesis and hematopoiesis. The initiation of the signal tranduction starts by the binding of a BMP to a corresponding set of BMP receptors. Using image cross-correlation spectroscopy, we show that the BMP receptors BRIa and BRII colocalize with caveolin-1 isoforms alpha and beta on the cell surface. BRIa colocalizes predominantly with the caveolin-1 alpha isoform. Coexpression of BRII leads to a redistribution of BRIa into domains enriched in caveolin-1 beta. After stimulation with BMP-2, BRIa moves back into the region with caveolin-1 alpha. BRII is expressed in regions enriched in caveolin-1 alpha and beta. Stimulation of cells with BMP-2 leads to a redistribution of BRII into domains enriched in caveolin-1 alpha. Immunoprecipitation studies using transfected COS-7 cells indicate that BRII binds to caveolin-1 alpha and beta. The binding of BRII to caveolin-1 was verified using A431 cells. Stimulation of starved A431 cells with BMP-2 lead to a release of caveolin-1 from the BMP receptors. We show further that the caveolin-1 beta isoform inhibits BMP signaling whereas the alpha isoform does not.

Links

PubMed Online version:10.1242/jcs.01402

Keywords

Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein Receptors; Bone Morphogenetic Protein Receptors, Type I; Bone Morphogenetic Protein Receptors, Type II; Bone Morphogenetic Proteins/pharmacology; COS Cells; Caveolin 1; Caveolins/genetics; Caveolins/metabolism; Cell Line, Tumor; Cercopithecus aethiops; Culture Media, Serum-Free/pharmacology; Epithelial Cells/drug effects; Epithelial Cells/metabolism; Humans; Protein Binding; Protein Isoforms/genetics; Protein Isoforms/metabolism; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Receptors, Growth Factor/genetics; Receptors, Growth Factor/metabolism; Signal Transduction/physiology; Transfection; Transforming Growth Factor beta/pharmacology; Up-Regulation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:BMR1A

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CAV1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13873

F

Seeded From UniProt

complete

HUMAN:CAV1

located_in

GO:0005901: caveola

ECO:0000303: author statement without traceable support used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BMPR2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q03135-2

F

Seeded From UniProt

complete

HUMAN:BMPR2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q03135-1

F

Seeded From UniProt

complete

HUMAN:BMPR2

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CAV1

involved_in

GO:0030514: negative regulation of BMP signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CAV1

involved_in

GO:0009267: cellular response to starvation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CAV1

part_of

GO:0005901: caveola

ECO:0000303: author statement without traceable support used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BMPR2

involved_in

GO:0009267: cellular response to starvation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BMPR2

colocalizes_with

GO:0005901: caveola

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BMPR2

part_of

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BMR1A

colocalizes_with

GO:0005901: caveola

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BMR1A

part_of

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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