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Title: Molecular interactions and cellular functions of the vasodilator stimulated phosphoprotein (VASP)
Author: Price, Caroline J.
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2000
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The vasodilator stimulated phosphoprotein (VASP) is associated with focal adhesions, actin microfilaments and regions of highly dynamic membrane activity in cells. VASP binds to the G-actin-binding protein profilin which regulates actin polymerisation. It also binds to the Listeria monocytogenes surface protein Act A and recruits profilin to the bacterial surface, thereby promoting efficient actin polymerisation for movement of the bacteria. It has been postulated that a cellular homologue of the Act A protein may exist which recruits VASP to cell membrane surfaces. Here, binding of VASP to a potential Act A homologue was investigated. It was found that VASP binds to the cytoskeletal protein vinculin via a similar sequence to the VASP-binding domain in Act A. The significance of the interaction of VASP with vinculin and profilin in actin filament assembly at cell membranes was then investigated. Various deletion constructs of VASP were expressed in cells and the effect on F-actin organisation and cortical activity examined. VASP overexpression in cells caused an increase in membrane ruffling activity and this effect was independent of profilin-binding. This suggests that VASP promotes membrane actin filament assembly through an alternative mechanism. Recently it has been shown that VASP is able to nucleate actin filament assembly in vitro, consistent with this theory. Overexpression of VASP also caused the formation of large stress fibres, through a short region in the C-terminus of the protein. A potential interaction of this region was investigated but no ligand identified. It is now known that this region mediates binding and bundling of F-actin. A model is put forward in which VASP bundles and tethers newly-formed actin filaments in nascent focal complexes at the leading edge of cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available