dc.contributor.author | Elsenpeter, Ryan Lee | eng |
dc.date.issued | 2012-08-27 | eng |
dc.date.submitted | 2012 Summer | eng |
dc.description | Title from PDF of title page, viewed on August 27, 2012 | eng |
dc.description | Dissertation advisor: Michael Plamann | eng |
dc.description | Vita | eng |
dc.description | Includes bibliographic references (p. 130-143) | eng |
dc.description | Thesis (Ph.D.)--School of Biological Sciences. University of Missouri--Kansas City, 2012 | eng |
dc.description.abstract | Eukaryotic cells utilize multiple molecular motor proteins to accomplish
intracellular transport. The two microtubule based motors, kinesin and cytoplasmic
dynein, work in concert to move cargoes outward and inward, respectively, in the cell. In
polarized cells, molecular motors are of even greater importance due to a need for long
distance transport and maintenance of proper polarity. Although there exists numerous
forms of kinesin for anterograde transport, only a single cytoplasmic form of dynein
carries out the functions of retrograde transport. To accomplish its tasks, dynein makes
use of multiple subunits and accessory proteins, including heavy chains, light chains,
intermediate chains, light intermediate chains, and dynactin to form a motor complex of
several megadaltons. The last two thirds of the dynein heavy chains contain the main
motor unit required for force production, while the N-terminal tail region of the dynein
heavy chain along, with other dynein components, aid in cargo binding. Force
production and microtubule-based movement is accomplished by coordinating ATP
hydrolysis in the motor heads with a microtubule-binding domain. The tail domain
allows for both homodimerization of motor heads as well as binding of other dynein
subunits. In this work, various genetic, cell biology, and biochemical methods were used to
study cytoplasmic dynein in the filamentous fungus, Neurospora crassa. Numerous
dynein heavy chain mutants were isolated previously from a genetic screen, with a subset
located to the C-terminal region, which were the focal point of this work. To explore the
mechanism by which these mutations affect dynein function, both intragenic and
extragenic suppressors were identified. A novel extragenic suppressor of dynein
mutations was discovered, a gene encoding a putative E3 ubiquitin ligase with homologs
present in higher organisms, including humans. Mutation or deletion of the suppressor
gene results in restoration of wild type-like growth and in vivo dynein localization for
each of the C-terminal dynein heavy chain mutants, as well as certain other dynein heavy
chain mutants. Results suggest that the activity of this protein affects interaction of
dynein heavy chain with dynein intermediate chain and likely is a regulator of dynein
motor assembly. | eng |
dc.description.tableofcontents | Introduction -- Materials and methods -- Results -- Discussion | eng |
dc.format.extent | 144 pages | eng |
dc.identifier.uri | http://hdl.handle.net/10355/14953 | eng |
dc.publisher | University of Missouri--Kansas City | eng |
dc.subject.lcsh | Dynein | eng |
dc.subject.lcsh | Neurospora crassa | eng |
dc.subject.mesh | Ubiquitin-Protein Ligases | eng |
dc.subject.other | Dissertation -- University of Missouri--Kansas City -- Biology | eng |
dc.title | Involvement of a specific ubiquitin ligase in the assembly of the dynein motor in the filamentous fungus Neurospora crassa | eng |
dc.type | Thesis | eng |
thesis.degree.discipline | Cell Biology and Biophysics (UMKC) | eng |
thesis.degree.discipline | Molecular Biology and Biochemistry (UMKC) | eng |
thesis.degree.grantor | University of Missouri--Kansas City | eng |
thesis.degree.level | Doctoral | eng |
thesis.degree.name | Ph.D. | eng |