Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.651896
Title: Characterization of Invadolysin in flies and human cells : new insights into a novel, essential metalloprotease
Author: Gururaja Rao, Shubha
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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Abstract:
I have analysed the functions of a novel, conserved metalloprotease named Invadolysin, previously reported by the Heck laboratory to be involved in mitosis and cell migration. I carried out a second site non-complementation screen in Drosophila melanogaster to identify the interactors of Invadolysin utilizing the availability of a collection of genome-wide deficiency stocks. As a result of this screen, I identified non-stop, a ubiquitin protease, as a genetic interactor of invadolysin.  I characterized similar mutant phenotypes of invadolysin and non-stop and showed that the abnormal chromosomal architecture observed in both mutants might be a result of histone ubiquitination. I also investigated the involvement of Invadolysin in Notch pathway. The Notch extracellular domain levels were normal in the invadolysin mutants, but the intracellular domain levels were greatly reduced suggesting that the Notch pathway was inactive, or compromised. The levels of the Notch ligand Delta were abnormally high in invadolysin mutants, suggesting a block of Notch activity through cis-inactivation due to a possible failure in endocytosis of the Delta ligand. In human cells, I showed that Invadolysin co-localized with Rab11 and Itch proteins, which have been shown to influence the Notch pathway. Considering the possible involvement of Invadolysin in Delta endocytosis, I examined the co-localisation of Invadolysin with endocytosis machinery in human cells. I found that Invadolysin rings partially localised with Caveolin-1, and the caveolar endocytosis marker cholera toxin B was found inside the Invadolysin ring-like structures, suggesting that the inner region of Invadolysin rings might be a lipid based entity. When the lipid droplet marker BODIPY was utilized with Invadolysin, I established that Invadolysin surrounds lipid droplets.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.651896  DOI: Not available
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