{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/1021"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/1021","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"TDP-43 Is Directed to Stress Granules by Sorbitol, a Novel Physiological Osmotic and Oxidative Stressor","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Dewey, Colleen Marie"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Yu, Gang"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-07-20T18:46:59Z","date_published":"2012-07-20T18:46:59Z","updated_at":"2026-07-24T05:52:36Z","subjects":["Cytoplasmic Granules","DNA-Binding Proteins","Sorbitol"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["811136850"],"render_values":[{"text":"811136850","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/1021","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Yu, Gang"]},{"key":"dc:creator","label":"Author","values":["Dewey, Colleen Marie"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2012-07-20T18:46:59Z","2012-07-20"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cytoplasmic Granules","DNA-Binding Proteins","Sorbitol"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/1021","811136850"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["TDP-43 Is Directed to Stress Granules by Sorbitol, a Novel Physiological Osmotic and Oxidative Stressor"]}]}],"canonical_facts":{"dc:contributor":["Yu, Gang"],"dc:creator":["Dewey, Colleen Marie"],"dc:date":["2012-07-20T18:46:59Z","2012-07-20"],"dc:description":["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."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/1021","811136850"],"dc:language":["en"],"dc:subject":["Cytoplasmic Granules","DNA-Binding Proteins","Sorbitol"],"dc:title":["TDP-43 Is Directed to Stress Granules by Sorbitol, a Novel Physiological Osmotic and Oxidative Stressor"],"dc:type":["Thesis","Text"]},"updated_at":"2026-07-24T05:52:36Z"}