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Caveolin-1 polarization in transmigrating endothelial cells requires binding to intermediate filaments

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Abstract

Caveolin-1 influences cell migration through multiple signaling pathways. In a previous report, we have shown that caveolin-1 is polarized in three-dimensional migrating endothelial cells (EC), and that caveolin-1 accumulation at the front of transmigrating cells requires the phosphorylatable Tyr14 residue of caveolin-1. Immuno-electron microscopy further indicated that caveolin-1 was distributed along cytoskeletal structures in the anterior of transmigrating EC [Parat MO, Anand-Apte B, Fox PL (Mol Biol Cell 14:3156–3168, 2003)]. In the present study, we investigate whether caveolin-1 interacts with intermediate filaments (IF) and whether this interaction is required for caveolin-1 polarization in transmigrating cells. The distribution of vimentin is polarized in cells traversing a filter pore and overlaps with the distribution of caveolin-1, which accumulates in the cell front. In vivo sprouting EC also exhibit an anterior polarization of these two proteins. Furthermore, caveolin-1 co-purifies with intermediate filaments, suggesting an interaction between caveolin-1 and IF. Vimentin-deficient SW13 cells exhibit a dramatically altered polarization of caveolin-1-GFP, which no longer accumulates in the protruding cell extension. In addition, the Tyr14 residue of caveolin-1 is required for co-purification of the protein with IF. Taken together, our results show that caveolin-1 Tyr14 is necessary for binding to intermediate filaments, which in turn is required for anterior polarization of caveolin-1 in transmigrating cells.

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Acknowledgements

This work was supported by American Heart Association Post Doctoral Fellowship 0525466B (to V.S.), and by American Cancer Society grant RSG-07-292-01-CSM (to M.-O.P.).

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Author notes

  1. Marie-Odile Parat

    Present address: School of Pharmacy, University of Queensland, St. Lucia, QLD, 4072, Australia

Authors and Affiliations

  1. Department of Anesthesiology Research, Cleveland Clinic, NE63, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Virginie Santilman, JoAnne Baran & Marie-Odile Parat

  2. Department of Ophthalmic Research, Cleveland Clinic, Cleveland, OH, USA

    Bela Anand-Apte

  3. Department of Pathology, University of Colorado Health Sciences Center, Denver, CO, USA

    Robert M. Evans

  4. Department of Outcomes Research, Cleveland Clinic, Cleveland, OH, USA

    Marie-Odile Parat

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  1. Virginie Santilman
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Correspondence to Marie-Odile Parat.

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Santilman, V., Baran, J., Anand-Apte, B. et al. Caveolin-1 polarization in transmigrating endothelial cells requires binding to intermediate filaments. Angiogenesis 10, 297–305 (2007). https://doi.org/10.1007/s10456-007-9083-z

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  • DOI: https://doi.org/10.1007/s10456-007-9083-z

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