{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/10075"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/10075","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"ER-PM Junction Proteins and Their Roles in Regulating Cell Homeostasis and Signaling","abstract":"Pages x-xiii are misnumbered as pages xi-xiv, page xiv is misnumbered as page 1, and pages 1-96 are misnumbered as pages 2-97.","abstract_html":"Pages x-xiii are misnumbered as pages xi-xiv, page xiv is misnumbered as page 1, and pages 1-96 are misnumbered as pages 2-97.","abstract_has_math":false,"creators":["Quintanilla, Carlo Giovanni"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Henne, W. Mike","Schmid, Sandra","Tu, Benjamin","Liou, Jen"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023-06-07T18:16:58Z","date_published":"2023-06-07T18:16:58Z","updated_at":"2026-07-24T05:52:17Z","subjects":["Endoplasmic Reticulum","Membrane Proteins"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1381370405"],"render_values":[{"text":"1381370405","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/10075","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Henne, W. Mike","Schmid, Sandra","Tu, Benjamin","Liou, Jen"]},{"key":"dc:creator","label":"Author","values":["Quintanilla, Carlo Giovanni"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2023-06-07T18:16:58Z","2021-05","2021-05-01T05:00:00.000Z","May 2021","2023-06-07T18:16:59Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Endoplasmic Reticulum","Membrane Proteins"]}]},{"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/2152.5/10075","1381370405"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Pages x-xiii are misnumbered as pages xi-xiv, page xiv is misnumbered as page 1, and pages 1-96 are misnumbered as pages 2-97.","Homeostatic regulation of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate (PIP2) in receptor-stimulated cells is a critical step in the phosphoinositide cycle (PI-Cycle). This regulatory feedback mechanism is mediated by the lipid transfer protein (LTP) Nir2. Nir2 is dynamically recruited to endoplasmic reticulum-plasma membrane (ER-PM) junctions to facilitate replenishment of PM PIP2 hydrolyzed during receptor-mediated signaling. However, our knowledge regarding the activation and sustainment of Nir2-mediated replenishment of PM PIP2 is limited. The work presented in this dissertation, describes the functions of Nir1, a previously unidentified ER-PM junction tether and regulator of Nir2 and PM PIP2 replenishment. Manipulation of Nir1 levels in live cells via overexpression or transient knockdown drives remodeling of ER-PM junction properties. Additionally, Nir1 potentiates Nir2 targeting to ER-PM junctions during receptor-mediated signaling and is required for efficient PM PIP2 replenishment. Importantly, I found that Nir1 localization at ER-PM junctions is a requirement for Nir2 potentiation, highlighting the importance of this subcellular site in regulating the PI-Cycle. The Live-cell and biochemical analysis revealed that Nir1 interacts with Nir2 via a region between the FFAT motif and the DDHD domain. Lastly, I describe a novel localization of Nir proteins near the nucleus and demonstrate the requirement of the minimally characterized domain, DDHD. In summary, the results from these studies identify Nir1 as a novel ER-PM junction tether as well as a positive regulator of the PI-Cycle and of the LTP, Nir2. My observations of Nir proteins near the nucleus implicate a novel subcellular site for phosphoinositide metabolic regulation beyond ER-PM junctions."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["ER-PM Junction Proteins and Their Roles in Regulating Cell Homeostasis and Signaling"]}]}],"canonical_facts":{"dc:contributor":["Henne, W. Mike","Schmid, Sandra","Tu, Benjamin","Liou, Jen"],"dc:creator":["Quintanilla, Carlo Giovanni"],"dc:date":["2023-06-07T18:16:58Z","2021-05","2021-05-01T05:00:00.000Z","May 2021","2023-06-07T18:16:59Z"],"dc:description":["Pages x-xiii are misnumbered as pages xi-xiv, page xiv is misnumbered as page 1, and pages 1-96 are misnumbered as pages 2-97.","Homeostatic regulation of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate (PIP2) in receptor-stimulated cells is a critical step in the phosphoinositide cycle (PI-Cycle). This regulatory feedback mechanism is mediated by the lipid transfer protein (LTP) Nir2. Nir2 is dynamically recruited to endoplasmic reticulum-plasma membrane (ER-PM) junctions to facilitate replenishment of PM PIP2 hydrolyzed during receptor-mediated signaling. However, our knowledge regarding the activation and sustainment of Nir2-mediated replenishment of PM PIP2 is limited. The work presented in this dissertation, describes the functions of Nir1, a previously unidentified ER-PM junction tether and regulator of Nir2 and PM PIP2 replenishment. Manipulation of Nir1 levels in live cells via overexpression or transient knockdown drives remodeling of ER-PM junction properties. Additionally, Nir1 potentiates Nir2 targeting to ER-PM junctions during receptor-mediated signaling and is required for efficient PM PIP2 replenishment. Importantly, I found that Nir1 localization at ER-PM junctions is a requirement for Nir2 potentiation, highlighting the importance of this subcellular site in regulating the PI-Cycle. The Live-cell and biochemical analysis revealed that Nir1 interacts with Nir2 via a region between the FFAT motif and the DDHD domain. Lastly, I describe a novel localization of Nir proteins near the nucleus and demonstrate the requirement of the minimally characterized domain, DDHD. In summary, the results from these studies identify Nir1 as a novel ER-PM junction tether as well as a positive regulator of the PI-Cycle and of the LTP, Nir2. My observations of Nir proteins near the nucleus implicate a novel subcellular site for phosphoinositide metabolic regulation beyond ER-PM junctions."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/10075","1381370405"],"dc:language":["en"],"dc:subject":["Endoplasmic Reticulum","Membrane Proteins"],"dc:title":["ER-PM Junction Proteins and Their Roles in Regulating Cell Homeostasis and Signaling"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:17Z"}