title: Endoplasmic reticulum size and shape control in Saccharomyces cerevisiae
creator: Papagiannidis, Dimitrios
subject: ddc-500
subject: 500 Natural sciences and mathematics
subject: ddc-570
subject: 570 Life sciences
description: Cells resize and reshape their organelles in response to changing physiological demands.   This thesis focuses on the endoplasmic reticulum (ER), an organelle which, depending on cell   type and physiological conditions, displays remarkable adaptability in both size and shape.   Although much is known about the role of proteins in ER morphogenesis, the mechanisms   controlling the biogenesis of its membrane, and hence size, are unclear. In this work, I build   upon a genetic screen performed to identify genes involved in ER expansion in the budding   yeast, Saccharomyces cerevisiae, and I focus on the poorly characterised ER membrane   protein Ice2p. I show that Ice2p is required for and promotes ER expansion, and that it does   so independently of the central determinant of ER homeostasis, the unfolded protein   response (UPR). To further uncover the molecular role of Ice2p, I explore known genetic   interactions and discover that Ice2p opposes the activity of Pah1p, which is a conserved   phosphatidic acid phosphatase with a central role in the regulation of lipid synthesis in yeast.   Specifically, I show that Ice2p interacts with and inhibits the conserved Spo7p-Nem1p   complex, which normally dephosphorylates and activates Pah1p. By showing that Ice2p   cooperates with pathways transcriptionally controlling lipid synthesis, and with the UPR to   maintain cell homeostasis, I place Ice2 into a broader cellular context. Additionally, I present   preliminary data approaching the physiological conditions during which cells use Ice2p-Pah1p to control the size of their ER. Finally, in the last part of the thesis, I follow up on the   unexpected observation that the reticulon proteins, which are membrane proteins with a   central and conserved role in ER morphogenesis, form cytosolic puncta after prolonged ER   stress, a phenotype especially pronounced in cells lacking Ice2p. These data suggest that   there are mechanisms controlling the membrane association of reticulon proteins, and as an   extension ER shape. Overall, this thesis extends the understanding of mechanisms regulating   the biogenesis of ER membrane as well as its morphogenesis and provides the ground for   future work not only in yeast but also in higher eukaryotes.
date: 2022
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserver/31712/1/Papagiannidis_PhD_thesis.pdf
identifier: DOI:10.11588/heidok.00031712
identifier: urn:nbn:de:bsz:16-heidok-317121
identifier:   Papagiannidis, Dimitrios  (2022) Endoplasmic reticulum size and shape control in Saccharomyces cerevisiae.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/31712/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng