Mechano-sensing and caveolae
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Caveolae are small invaginations of the plasma membrane, and are especially abundant in the endothelial cells that line blood vessels, in adipocytes, and in muscle cells. We and others have shown that caveolae flatten out when cells are stretched, and that this flattening of membrane convolutions is likely to buffer mechanical tension within the plasma membrane. Cells lacking caveolae are more likely to rupture than cells with caveolae. There is good evidence that caveolae also transduce intracellular signals in response to mechanical force, as caveolae-dependent changes in gene transcription in cells undergoing repeated stretching have been reported. The goal of this project is to determine the molecular mechanisms that allow caveolae to sense and transduce mechanical cues at the plasma membrane. We will apply a range of biochemical, genetic and imaging techniques. Our lab has developed a range of CRISPR-edited cell lines expressing tagged versions of all known caveolar components, and complimentary gene knockout cell lines. These, along with new cell lines generated during the project, will be a key resource. The main biochemical approach that we will apply is proximity labelling, using BioID or similarly tagged versions of caveolar proteins in cells cells undergoing stretch. The project is flexible and may also, depending on circumstances, focus on related aspects of the cell biology of caveolae.