Biomedical subjects

Marie-Odile Parat

Publications and source records attributed to Marie-Odile Parat.

5 recordsLinked to original sources

PubMed2006

Caveolin-1 polarization in migrating endothelial cells is directed by substrate topology not chemoattractant gradient.

Polarization is a hallmark of migrating cells, and an asymmetric distribution of proteins is essential to the migration process. Caveolin-1 is highly polarized in migrating endothelial cells (EC). Several studies have shown caveolin-1 accumulation in the front of migrating EC while others report its accumulation in the EC rear. In this paper we address these conflicting results on polarized localization of caveolin-1. We find evidence for the hypothesis that different modes of locomotion lead to differences in protein polarization. In particular, we show that caveolin-1 is primarily localized in the rear of cells migrating on a planar substrate, but in the front of cells traversing a three-dimensional pore. We also show that a chemoattractant, present either as a gradient or ubiquitously in the medium, does not alter caveolin-1 localization in cells in either mode of locomotion. Thus we conclude that substrate topology, and not the presence of a chemoattractant, directs the polarization of caveolin-1 in motile ECs.

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PubMed2004

Oxidative stress, caveolae and caveolin-1.

Oxidative stress underlies a range of pathophysiological conditions. Reactive oxygen species are also generated intracellularly to serve as second messengers and some are linked to caveolae/raft signalling systems. The effect of oxidative stress on caveolin-1 expression, post-translational modifications, membrane trafficking and function are described.

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PubMed2004

A role for caveolae in cell migration.

Caveolae are specialized plasma membrane subdomains capable of transport and sophisticated compartmentalization of cell signaling. Numerous cell functions, including cell type-specific functions, involve caveolae and require caveolin-1, the major protein component of these organelles. Caveolae are particularly abundant in endothelial cells and participate in endothelial transcytosis, vascular permeability, vasomotor tone control, and vascular reactivity. Caveolin-1 drives the formation of plasma membrane caveolae and anchors them to the actin cytoskeleton, modulates cell interaction with the extracellular matrix, pulls together and regulates signaling molecules, and transports cholesterol. Via these functions, caveolin-1 might play an important role in cell movement through control of cell membrane composition and membrane surface expansion, polarization of signaling molecules and matrix proteolysis, and/or cytoskeleton remodeling. Caveolae and caveolin-1 are polarized in migrating endothelial cells, indicating they may play a role in cell motility. Several studies have shown that manipulation of caveolin-1 expression affects cell migration in a complex way. We are reviewing the current data and hypotheses in favor of an essential role for caveolae in cell migration.

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PubMed2003

Differential caveolin-1 polarization in endothelial cells during migration in two and three dimensions.

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 three dimensions during angiogenesis. We herein investigate differences in these modes of movement focusing on caveolae and their defining protein caveolin-1. Using a novel approach for morphological 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 seems to be released from caveolar structures in the cell rear and to relocalize at the cell front in a cytoplasmic form. In contrast, during planar movement caveolin-1 is concentrated at the rear of ECs, colocalizing 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 three dimensions uniquely exhibit dissociation of caveolin-1 from caveolae and phosphorylation-dependent relocalization to the cell front.

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PubMed2002

Oxidative stress inhibits caveolin-1 palmitoylation and trafficking in endothelial cells.

During normal and pathological conditions, endothelial cells (ECs) are subjected to locally generated reactive oxygen species, produced by themselves or by other vessel wall cells. In excess these molecules cause oxidative injury to the cell but at moderate levels they might modulate intracellular signalling pathways. We have investigated the effect of oxidative stress on the palmitoylation and trafficking of caveolin-1 in bovine aortic ECs. Exogenous H2O2 did not alter the intracellular localization of caveolin-1 in ECs. However, metabolic labelling experiments showed that H2O2 inhibited the trafficking of newly synthesized caveolin-1 to membrane raft domains. Several mechanisms potentially responsible for this inhibition were examined. Impairment of caveolin-1 synthesis by H2O2 was not responsible for diminished trafficking. Similarly, the inhibition was independent of H2O2-induced caveolin-1 phosphorylation as shown by the markedly different concentration dependences. We tested the effect of H2O2 on palmitoylation of caveolin-1 by the incorporation of [3H]palmitic acid. Exposure of ECs to H2O2 markedly inhibited the palmitoylation of caveolin-1. Comparable inhibition was observed after treatment of cells with H2O2 delivered either as a bolus or by continuous delivery with glucose and glucose oxidase. Kinetic studies showed that H2O2 did not alter the rate of caveolin-1 depalmitoylation but instead decreased the 'on-rate' of palmitoylation. Together these results show for the first time the modulation of protein palmitoylation by oxidative stress, and suggest a cellular mechanism by which stress might influence caveolin-1-dependent cell activities such as the concentration of signalling proteins and cholesterol trafficking.

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