TDP-43 Is Directed to Stress Granules by Sorbitol, a Novel Physiological Osmotic and Oxidative Stressor
dc.contributor.advisor | Yu, Gang | en |
dc.creator | Dewey, Colleen Marie | en |
dc.date.accessioned | 2012-07-20T18:46:59Z | |
dc.date.available | 2012-07-20T18:46:59Z | |
dc.date.issued | 2012-07-20 | |
dc.description.abstract | TDP-43, or TAR DNA-binding protein 43, is a pathological marker of a spectrum of neurodegenerative disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). TDP-43 is an RNA/DNA-binding protein implicated in transcriptional and post-transcriptional regulation. Recent work also suggests that TDP-43 associates with cytoplasmic stress granules, which are transient structures that form in response to stress. In this study, we establish sorbitol as a novel stressor that directs TDP-43 to stress granules in Hek293T cells and primary cultured glia. We quantify TDP-43 association with stress granules over time and show that stress granule association and size are dependent on the glycine-rich region of TDP-43, which harbors the majority of pathogenic mutations. Moreover, we establish that cells harboring wild-type and mutant TDP-43 have distinct stress responses: mutant TDP-43 forms significantly larger stress granules and incorporates into stress granules more early; in striking contrast, wild-type TDP-43 forms more stress granules over time, but granule size remains relatively unchanged. We propose that mutant TDP-43 alters stress granule dynamics, which may contribute to the progression of TDP-43 proteinopathies. | en |
dc.identifier.oclc | 811136850 | |
dc.identifier.uri | https://hdl.handle.net/2152.5/1021 | |
dc.language.iso | en | en |
dc.subject | Cytoplasmic Granules | en |
dc.subject | DNA-Binding Proteins | en |
dc.subject | Sorbitol | en |
dc.title | TDP-43 Is Directed to Stress Granules by Sorbitol, a Novel Physiological Osmotic and Oxidative Stressor | en |
dc.type | Thesis | en |
dc.type.material | Text | en |
thesis.date.available | 2014-01-14 | |
thesis.degree.department | Graduate School of Biomedical Sciences | en |
thesis.degree.discipline | Neuroscience | en |
thesis.degree.grantor | UT Southwestern Medical Center | en |
thesis.degree.level | Doctoral | en |
thesis.degree.name | Doctor of Philosophy | en |
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