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Title: The role of WASP-Interacting Protein (WIP) in regulating the assembly and function of podosomes
Author: Vijayakumar, Vineetha
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2013
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Podosomes are adhesion structures commonly found in migrating leukocytes of the monocytic lineage. The actin cytoskeletal organisation of podosomes is based on a Wiskott Aldrich Syndrome Protein (WASP) - Actin Related Protein 2/3 complex (Arp2/3) mediated mechanism. WASP is associated with WIP via its WH1 N-terminus domain, but very little is known of how WIP influences podosome function. This study reports for the first time that WASP Interacting Protein (WIP) is phosphorylated on tyrosine residues and that tyrosine phosphorylation of WIP is a trigger for release of WASP from the WIP-WASP complex. Using a knockdown approach together with expression of WIP phosphomimics the present study shows that in the absence of WIP-WASP binding, cellular WASP is rapidly degraded leading to disruption of podosomes and a failure of the cells to degrade an underlying matrix. In the absence of tyrosine phosphorylation of WIP, the WIP-WASP complex remains intact. Thus this study suggests that phosphorylation of WIP is a critical regulator of WASP stability and function as an actin nucleation promoting factor in monocytic leukocytes.
Supervisor: Jones, Gareth E. ; Wells, Claire Marie Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available