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Title: Regulation of microtubules by Patronin within Drosophila dendrites
Author: Brooks, Paul
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2020
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The nervous system of most animals is a highly complex network that transmits signals throughout the organism. The complexity of the human nervous system can, at times, appear inscrutable; therefore, it is practical to break it down into fewer components and to study a simplified, yet still complex analogue. This thesis utilises the fruit fly Drosophila melanogaster as a model to forward our understanding on neuronal development and maintenance. Neurons are the most modular of all cells, comprising of a cell body, axon and dendrites. The development and function of each compartment relies heavily on the cytoskeleton, a major component of which are microtubules, which are required for intracellular transport, as well as establishing neuronal morphology. In this thesis, I identify microtubule regulators that are necessary for the dendritic development of Drosophila sensory dendritic arborisation neurons, where I show that the minus-end targeting protein, Patronin, prevents unregulated minus-end growth within dendrites. Unlike in mammalian interphase cells, Drosophila Patronin does not function at Golgi within da neurons. Depletion of Patronin from class I da neurons results in dendrite over-branching and excessive growth of microtubules away from the soma. Given that most microtubules have their minus ends facing away from the soma in the dendrites of these neurons, I propose that the absence of Patronin leads to the unregulated growth of minus-ends away from the soma that invade terminal dendrites and prevent their retraction. I also find that that the microtubule depolymerising enzyme, Klp10A does not function in class I dendrites, and that overexpression is sufficient to rescue anterograde minus-end polymerisation that results from Patronin depletion. These findings are the first to show a role for Patronin in microtubule minus-end growth restriction in vivo, and further increase our understanding of microtubule regulation in the nervous system.
Supervisor: Conduit, Paul Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Patronin ; Microtubule ; Minus-end