Evolutionary history of clathrin-mediated endocytosis and the eisosome

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Evolutionary history of clathrin-mediated endocytosis and the eisosome

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dc.contributor.author Cibrario, Luigi en_US
dc.date.accessioned 2012-03-29T15:42:02Z en_US
dc.date.accessioned 2013-03-21T10:39:47Z
dc.date.issued 2011-08-01 en_US
dc.description.abstract Endocytosis is both an ancient and a diverse feature of the eukaryotic cell. Studying how it evolved can provide insight into the nature of the last common eukaryotic ancestor, and the diversification of eukaryotes into the known extant lineages. In this thesis, I present two studies on the evolution of endocytosis. In the first part of the thesis I report results from a large-scale, phylogenetic and comparative genomic study of clathrin-mediated endocytosis (CME). The CME pathway has been studied to a great level of detail in yeast to mammal model organisms. Several protein families have now been identified as part of the complex set of protein-protein and protein-lipid interactions which mediate endocytosis. To investigate how such complexity evolved, first, I defined the modular nature of the CME interactome (CME-I) by literature review, and then I carried out a systematic phylogenetic and protein domain architecture analysis of the proteins involved. These data were used to construct a model of the evolution of the CME-I network, and to map the expansion of the network's complexity to the eukaryotic tree of life. In the second part of the thesis, I present results from evolutionary and functional studies of the eisosome, a protein complex which has been proposed to regulate the spatial distribution of endocytosis in S. cerevisiae. The phylogeny of eisosomes components Pil1 and Lsp1 reported here, suggests that eisosomes are likely to have originated at the base of the fungi, and then diversified significantly via multiple gene duplications. I thus studied the localisation and function of Pil1 and Lsp1 homologues in Magnaporthe oryzae to investigate the role of eisosomes in filamentous fungi. Results suggests that eisosomes are linked with septal formation and integrity in M. oryzae, and that the septal specific Pil2 paralogue was lost in budding yeasts. Together, the data presented in this thesis describe the evolutionary history of a complex biological system, but also highlights the problem of asymmetry in the understanding of endocytic diversity in the eukaryotes. en_GB
dc.description.sponsorship BBSRC en_GB
dc.identifier.grantnumber BB/D526296/1 en_GB
dc.identifier.uri http://hdl.handle.net/10036/3484 en_US
dc.language.iso en en_GB
dc.publisher University of Exeter en_GB
dc.rights.embargoreason The data reported in the thesis have not been published yet in peer-reviewed journals. It is thus requested that access to the results remains restricted until the manuscripts in preparation are submitted for publication. en_GB
dc.subject Endocytosis en_GB
dc.subject Clathrin en_GB
dc.subject Eisosome en_GB
dc.subject Comparative genomics en_GB
dc.subject Phylogenetics en_GB
dc.subject Eukaryotic evolution en_GB
dc.subject Evolution of endomembrane system en_GB
dc.subject Interactome network en_GB
dc.subject Actin cytoskeleton en_GB
dc.subject Magnaporthe oryzae en_GB
dc.subject Septal integrity en_GB
dc.title Evolutionary history of clathrin-mediated endocytosis and the eisosome en_GB
dc.type Thesis or dissertation en_GB
dc.date.available 2013-05-01T03:00:30Z
dc.contributor.advisor Talbot, Nicholas J en_US
dc.publisher.department College of Life and Environmental Sciences en_GB
dc.type.degreetitle PhD in Biological Sciences en_GB
dc.type.qualificationlevel Doctoral en_GB
dc.type.qualificationname PhD en_GB


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