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Title: Molecular mechanisms of microtubule plus end regulation in Drosophila
Author: Dzhindzhev, Nikola S.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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Microtubule plus ends are occupied and controlled by a special group of proteins. The first microtubule plus end tracking protein to be described was the human CLIP- 170, a member of a conserved protein family. Despite of the large number of studies devoted to the CLIP proteins their function is still poorly understood, especially in the context of a developing metazoan organism. In order to study the function of CLIP-190 in Drosophila development, two P-element insertion alleles were characterised. They were found to be hypomorphic, decreasing the expression of the gene, which however, had no effect on fly viability or development. Other efforts to disrupt CLIP-190 demonstrated that flies are tolerant to substantial variations from the normal levels of the protein. Studies of the subcellular behaviour of CLIP-190 in Drosophila cell culture revealed its distinct localisation during the cell cycle. Its interphase microtubule plus end binding ability was found to depend on the presence of another microtubule regulator, EB1 and a direct interaction between the two proteins was demonstrated. In prometaphase CLIP-190 localised to unattached kinetochores, which depended on the dynein-dynactin complex and associated proteins. The cell cycle regulation on CLIP-190 was investigated and several possible regulators were tested. An RNAi screen in Drosophila cell culture was undertaken to identify new microtubule regulators. Proteins were selected on the basis of their ability to bind to microtubules or tubulin. Their systematic depletion followed by immunofluorescence examination of the microtubule cytoskeleton identified 3 proteins required for normal microtubule organisation. This study revealed the molecular mechanisms that control the localisation of CLIP-190 during the cell cycle and identified 3 new microtubule regulators. It will therefore increase our understanding of the microtubule regulation in Drosophila cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available