Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.814972
Title: The evolutionary origin of postsynaptic signalling machineries : insights from the single-celled sister group to the animals
Author: Hoffmeyer, T. T.
ISNI:       0000 0004 9356 033X
Awarding Body: University of Exeter
Current Institution: University of Exeter
Date of Award: 2020
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Abstract:
Choanoflagellates are a diverse monophyletic group of aquatic heterotrophic flagellates that form the sister group to the animals (Leadbeater, 2015). Genome surveys in two closely related choanoflagellate species – Salpingoeca rosetta and Monosiga brevicollis – showed that choanoflagellates and animals share many genes that are crucial for animal biology, including genes encoding proteins with functions at animal synapses (King et al., 2008; Alié and Manuel, 2010; Fairclough et al., 2013; Burkhardt et al., 2014). I surveyed 19 choanoflagellate transcriptomes (Richter et al., 2018) for the presence of putative homologs to a key set of synaptic proteins in order to extend our knowledge of the putative ancestral prerequisites for postsynaptic signalling machineries. Postsynaptic signalling machineries are crucial for signal reception and transduction as well as the regulation of signal transduction strength (Kennedy, 2000). Importantly, I could identify putative homologs to Shaker-like potassium channels, nitric oxide synthases and ionotropic glutamate receptors in several choanoflagellate species. The survey further showed that putative homologs of postsynaptic scaffolding proteins (Homer, Shank, and membrane associated guanylate kinases – MAGUKs including Dlg and MAGUK p55) occur in choanoflagellates that branch throughout the phylogenetic radiation of this group. The high degree of structural conservation in S. rosetta Dlg, and Homer homologs suggests that these proteins are of functional importance in choanoflagellates. Furthermore, my data indicate that the scaffolding function of both of these proteins is conserved in choanoflagellates. Combining ancestral protein reconstruction with in vitro binding assays, allowed me to establish that the capacity of Homer to bind its synaptic binding partner Shank presumably preceded the evolution of animals and choanoflagellates. Moreover, in an experiment using co-immunoprecipitation in combination with mass spectrometry analysis, I investigated in vivo S. rosetta Dlg interaction partners. I found evidence that the interaction between Dlg and MAGUK p55 might be conserved in choanoflagellates. This type of interaction was observed at animal postsynapses and tight junctions (Stucke et al., 2007; Rademacher et al., 2016). My data suggest that synaptic scaffolding complexes might have preceded the evolution of animals. Synaptic signalling machineries therefore presumably were built upon pre-existing structural scaffolds.
Supervisor: Burkhardt, P. ; Richards, T. A. ; Wakefield, J. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.814972  DOI: Not available
Keywords: synapse evolution ; postsynaptic scaffolding protein ; choanoflagellates ; transcriptome survey ; ancestral protein reconstruction ; isothermal titration calorimetry ; co-immunoprecipitation
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