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dc.contributor.authorDavis, Richard Croft
dc.date.accessioned2014-03-03T23:26:32Z
dc.date.available2014-03-03T23:26:32Z
dc.date.issued2005-12
dc.identifier.otherdavis_richard_c_200512_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/davis_richard_c_200512_phd
dc.identifier.urihttp://hdl.handle.net/10724/22899
dc.description.abstractHirano bodies are paracrystalline F-actin aggregations reported in various tissues. Their function and physiological effect is not understood as analysis has been limited to post mortem tissue. We have recently demonstrated that we can induce Hirano body formation in Dictyostelium discoideum as well as mammalian cells including primary neurons, HeLa, and mouse broblasts cells by expressing the carboxyl-terminal (CT) region (a.a. 124-295) of the 34 kDa actin bundling protein. Numerous cell lines were investigated and veried to have formed Hirano bodies using immunouorescence and transmission electron microscopy. Initial expression of CT induces a small fraction of cells to die via p53 regulated apoptosis. However, cells constitutively forming Hirano bodies are healthy and appear to have an advantage when exposed to different types of acute stresses. Cells with Hirano bodies, such as L broblasts, survive acute oxidative CTstress better than cells without Hirano bodies. Furthermore, the percentage of cells with Hirano bodies increases following the stress suggesting a possible relationship. Cells experiencing DNA damage induced by the topoisomerase II inhibitor, etoposide, have enhanced viability if they contain Hirano bodies. These experiments suggest that Hirano bodies confer an adaptive advantage to cells containing the F-actin inclusions. As very little is known about the dynamics of Hirano bodies, investigations evaluating the dynamics of these inclusions in cultured mammalian cells were done. Cells constitutively expressing CT-GFP reveal a dynamic process that leads to the aggregation. This dynamic Àux requires an intact microtubule network. Evaluation of the small particle movement provided insight into the rates of movement that were consistent with active transport. Transmission electron micrographs indicate that Hirano bodies becomes membrane enclosed, consistent with degradation by autophagy, and that the structural order of Hirano bodies is altered in cells treated with inhibitors of ubiquitin-dependent protein degradation.
dc.languageeng
dc.publisheruga
dc.rightsOn Campus Only
dc.subjectF-Actin
dc.subjectHirano bodies
dc.subjectProtein inclusion
dc.subjectNeurodegeneration
dc.subjectMammalian cell
dc.subjectModel system
dc.subjectDynamics
dc.subjectApoptosis
dc.subjectAggregation
dc.subjectOxidative stress
dc.subjectTime Lapse Microscopy
dc.subjectCell culture
dc.titleInvestigation of structure/composition, physiological effects, and dynamics of Hirano bodies
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentCellular Biology
dc.description.majorCellular Biology
dc.description.advisorMarcus Fechheimer
dc.description.committeeMarcus Fechheimer
dc.description.committeeMark Farmer
dc.description.committeeJames Lauderdale
dc.description.committeeCharles Keith
dc.description.committeeKelley Moremen


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