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A more recent version of this article appeared on August 1, 2003
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Submitted on November 22, 2002
Revised on March 27, 2003
Accepted on April 17, 2003
1 Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
2 Cole Eye Institute, The Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
* Corresponding author. E-mail address: foxp{at}ccf.org.
Endothelial cell (EC) migration is a critical event during multiple physiological and pathological processes. ECs move in the plane of the endothelium to heal superficially injured blood vessels but migrate in 3-dimensions during angiogenesis. We here investigate differences in these modes of movement focusing on caveolae, and their defining protein caveolin-1. Using a novel approach for morphologic analysis of transmigrating cells, we show that ECs exhibit a polarized distribution of caveolin-1 when traversing a filter pore. Strikingly, in these cells caveolin-1 appears to be released from caveolar structures in the cell rear, and to re-localize at the cell front in a cytoplasmic form. In contrast, during planar movement caveolin-1 is concentrated at the rear of ECs, co-localizing with caveolae. The phosphorylatable Tyr14 residue of caveolin-1 is required for polarization of the protein during transmigration but does not alter polarization during planar movement. Palmitoylation of caveolin-1 is not essential for redistribution of the protein during either mode of movement. Thus, ECs migrating in 3-dimensions uniquely exhibit dissociation of caveolin-1 from caveolae and phosphorylation-dependent relocalization to the cell front.
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