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Title: The role of cavins in the biogenesis of caveolae
Author: Hansen, C. G.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2010
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Caveolae are 60-100 nm omega-shaped invaginations of the plasma membrane. In a thorough literature search, in combination with some basic bioinformatics data, a new family of four caveolar proteins was identified. I have shown that this family is important for caveolar morphology and function. This family is now in the process of being renamed as cavins. The functional relationship between two of the cavins was characterised in detail using biochemical, cell biological and imaging approaches. Loss of either Cavin1 or Cavin2 expression leads to a concomitant loss of the other member of this pair of cavins, and subsequently causes a loss of caveolae. Cavin2 binds directly to Cavin1 and recruits Cavin1 to caveolar membranes. Over-expression of Cavin2, unlike Cavin1, induces deformation of caveolae and extensive tabulation of the plasma membrane. We therefore conclude that Cavin2 is a membrane curvature-inducing component in caveolae. The B-subunit of shiga toxin (STxB) has recently been reported to induce membrane tubular structures for its uptake into cells. I found that membrane tubes induced by STxB also originate from caveolae, and that STxB co-localizes extensively with both Cavin2 and caveolin1. Loss of Cavin1, Cavin2 or caveolin1 reduces the propensity of STxB to induce membrane tabulation. The tubes induced by STxB in cells therefore appear to reflect the interaction of toxin-glycosphingolipid complexes with caveolar proteins. Interestingly, the cavin molecules have a tissue-specific expression and as prime regulators of caveolae, they therefore provide a link that could explain why caveolae have been claimed to have a wide variety of different functions in so many different tissues. I have carried out an initial characterisation to dissect the cavin complex at the molecular level. Preliminary data suggests a direct functional link between the cavin molecules, and thereby caveolae, to both the cytoskeleton and the nucleus.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available