Volume 126, 2004

Caveolin-1 isoform reorganization studied by image correlation spectroscopy

Abstract

Caveolae are small, flask shaped invaginations in the cell membrane. They are thought to play a crucial role in cell signaling, endocytosis and intracellular cholesterol transport. Caveolin-1, 2 and 3 are key proteins, which are important for the formation of the invaginations on the cell surface. Caveolin-1 exists in two isoforms: caveolin-1 alpha (α) and caveolin-1 beta (β). Little is known about the difference between these two isoforms, and less in known about their role in cell signaling. Bone morphogenetic proteins (BMPs) are a subfamily of the TGF beta superfamily and their response is mediated by serine/threonine kinase receptors. Epidermal growth factor (EGF) is known to signal through tyrosine kinase receptors of the ErbB family. Here we report on the aggregation and association of caveolin-1 isoforms with these receptors and the effect of BMP and EGF activation on caveolin-1 distribution in A431 cells. Our data, obtained by application of a family of image correlation spectroscopy tools, indicate that BMP and EGF stimulation lead to a rearrangement of the caveolin-1 isoforms on the cell surface. BMP as well as EGF stimulation leads to a rearrangement of the caveolin-1 β isoform into domains enriched in the caveolin-1 α isoform. We further show that about 20–30% of the caveolin-1 present at the surface of the cells co-localize with the EGF and BMP receptors. Using a reporter gene assay sensitive to the activation of the BMP pathway, we show that overexpression of caveolin-1 β inhibits signaling. Our data suggest that the two isoforms of caveolin-1 play different roles on the cell surface and that caveolae are dynamic structures.

Article information

Article type
Paper
Submitted
02 May 2003
Accepted
11 Jul 2003
First published
15 Oct 2003

Faraday Discuss., 2004,126, 185-195

Caveolin-1 isoform reorganization studied by image correlation spectroscopy

A. Nohe, E. Keating, C. Loh, M. T. Underhill and N. O. Petersen, Faraday Discuss., 2004, 126, 185 DOI: 10.1039/B304943D

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