Investigating the role of the putative lipid transport protein Fmp27 at ER-PM membrane contact sites
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Sridhar, Vaishnavi
issued: 2025-04-30T07:00:00Z
issued: 2023
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Eukaryotic organelle membranes are composed of lipids and proteins. Most lipid precursors are synthesized in the endoplasmic reticulum (ER) and are transported to other membranes. Transport can proceed either via the vesicular or the non-vesicular route, primarily via lipid transport proteins at membrane contact sites (MCSs). MCSs are sites of close apposition between organelle membranes, which are present in eukaryotes including plants, fungi and animals. These sites are maintained by protein tethers, which function in lipid transport, maintenance of membrane integrity, membrane biogenesis and ion regulation. One such protein tether, Vps13, is highly conserved and functions as a bulk lipid transporter at many MCSs. Bulk transport of lipids is required to confer rapid changes in lipid composition or for membrane elongation, such as in case of generation of prospore membranes or for autophagosome formation or during endocytosis. At ER-PM MCSs, Vps13-like proteins could function in membrane elongation during endocytosis, thus making it important to identify Vps13-like proteins at these sites. I identified an uncharacterized protein Fmp27 and its paralog Ypr117w, which have secondary structure similarities to Vps13, with a potential role in lipid homeostasis at ER-PM MCSs. Fmp27 is a well conserved protein, and its mammalian ortholog is overexpressed in breast cancer, whereas its fly and plant orthologs are implicated in organismal development. I found that Fmp27 is anchored to the ER and localizes to ER-PM cortical sites. Furthermore, I identified an interacting partner, Ybl086c, which binds to Fmp27 and recruits it to these cortical sites via a conserved region in its C-terminus. I found that Fmp27/Ypr117w and Ybl086c are not required for the growth of cells in response to various stresses such as temperature, salt, osmolarity and detergents. Using fluorescent lipid probes, I found that these proteins do not have a clear role in the distribution of the glycerophospho…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/84436
note: 1 Investigating the role of the putative lipid transport protein Fmp27 at ER-PM membrane contact sites by Vaishnavi Sridhar BS-MS (Indian Institute of Science Education and Research, Mohali) 2017 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in The Faculty of Graduate and Postdoctoral Studies (Cell and Developmental Biology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2023 ©Vaishnavi Sridhar, 2023 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Investigating the role of the putative lipid transport protein Fmp27 at ER-PM membrane contact sites. submitted by Vaishnavi Sridhar in partial fulfilment of the requirements for the degree of Doctor of Philosophy In Cell and Developmental Biology Examining Committee: Additional Supervisory Committee Members: Dr. Abel Rosado, Associate Professor, Botany, UBC Supervisory Committee Member Dr. Elizabeth Conibear, Professor, Medical Genetics, UBC Supervisor Dr. Christopher Loewen, Professor, Cell and Developmental Biology, UBC Supervisory Committee Member Dr. Ivan Robert Nabi, Professor, Cell and Developmental Biology, UBC Supervisory Committee Member Dr. Franck Duong, Professor, Biochemistry and Molecular Biology, UBC University Examiner Dr. Calvin Yip, Associate Professor, Biochemistry and Molecular Biology, UBC University Examiner iii Abstract Eukaryotic organelle membranes are composed of lipids and proteins. Most lipid precursors are synthesized in the endoplasmic reticulum (ER) and are transported to other membranes. Transport can proceed either via the vesicular or the non-vesicular route, primarily via lipid transport proteins at membrane contact sites (MCSs). MCSs are sites of close apposition between organelle membranes, which are present in eukaryotes including plants, fungi and animals. These sites are maintained by protein tethers, which…
has type: Thesis/Dissertation
date issued: 2023-05
is shown at: 10.14288/1.0431392
language: eng
degree discipline: Cell and Developmental Biology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Conibear, Elizabeth
type: Text
identifier URI: http://hdl.handle.net/2429/84436