Regulation of Microtubules by Patronin within Drosophila Dendrites

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.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2020

Author dc:creator

• Brooks, Paul

Advisor dc:contributor.advisor

• Conduit, Paul

• Patronin
• Microtubule
• Minus-end

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/3c25ca86-57ba-4009-b488-b7b3bab6e955/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

en

Author Identifier

0000-0002-7822-1191

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/300659