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Proteomic and anatomical characterisation of Drosophila MAGUK-associated signalling complexes

Understanding the molecular composition of the synapse is one of the ongoing problems in neuroscience. The synaptic proteome consists of about 1100 proteins, most of which are organised into complexes. Understanding the composition and function of these complexes is important for understanding the mechanisms and pathways of diseases which these protein complexes are involved in determining the sub-cellular localisation of these proteins and also their spatial distribution in the nervous system may lead to important insights into the function of such protein complexes thus furthering our understanding of the function and diseases of the nervous system. Neuro-proteomics has led to identification of an NMDA receptor complex (also called MAGUK-associated signalling complex (MASC)) which has been extensively studied in mouse. It consists of ~186 proteins in mouse and represents 10 different functional classes of proteins. Drosophila offers an opportunity to study this complex in more detail because it is 50% less complex while still maintaining all the functional classes of proteins. Since the fundamental structure and principles of neuronal function are conserved between vertebrates and Drosophila the physiology and molecular biology of disease can be better resolved in this simple organism. Here I present an effort to characterise the MASC complex in Drosophila and present the molecular composition of the MASC complex in Drosophila. I will present an anatomical map of the complex in the fly brain and also show that there is significantly high conservation of this complex between Drosophila and mouse. Two different approaches have been used in this thesis to study the molecular composition of this complex give results which are in partial agreement with each other. Importantly it provides an evaluation of these two methods and indicates that they can be used to study molecular complexes in Drosophila.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:586491
Date January 2013
CreatorsMalik, Bilal Rashid
ContributorsArmstrong, Douglas; Grant, Seth
PublisherUniversity of Edinburgh
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://hdl.handle.net/1842/8147

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