Characterisation of a novel interactor of the Ena/VASP family of proteins and the Scar/WAVE complex

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Cell migration is an essential process during embryonic development and its deregulation can cause developmental defects and contribute to tumour metastasis. Actin polymerisation drives cell migration by pushing the plasma membrane at the leading edge forward. Actin filament elongation is regulated by the Ena/VASP proteins and branched actin nucleation is regulated by a variety of protein family and complexes, including the Arp2/3 and Scar/WAVE complexes. A bioinformatics screen for novel interactors of the Ena/VASP family of proteins revealed a previously uncharacterised protein. We found that this novel protein interacts with all three family members of the Ena/VASP proteins via two Ena/VASP-binding sites, with preferential binding to Mena. Furthermore, we also found that the novel protein interacts with the Scar/WAVE complex, and this interaction is partially mediated via the Abi subunit of the complex. Finally, data in this thesis suggests that this protein regulates cell migration as determined via random migration assays, where we observed that a reduction of the novel protein correlates with a reduction in the speed of migrating cells. We propose that this protein is a novel regulator of cell migration, possibly via its interaction with the Ena/VASP family of proteins and the Scar/WAVE complex.
Date of Award1 May 2019
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorMatthias Krause (Supervisor) & Vicky Sanz Moreno (Supervisor)

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