Visa enkel post

dc.contributor.authorAhmadpour, Doryaneh
dc.date.accessioned2012-05-02T08:31:01Z
dc.date.available2012-05-02T08:31:01Z
dc.date.issued2012-05-02
dc.identifier.isbnISBN 978-91-628-8461-1
dc.identifier.urihttp://hdl.handle.net/2077/28374
dc.description.abstractAbstract Cells constantly encounter stress due to alterations in the external milieu or internal parameters. However, cells are robust to such changes and maintain homeostasis. Using the yeast Saccharomyces cerevisiae as a model organism, we attempted to elucidate aspects of homeostasis and robustness at both molecular and systems levels. At the molecular level, we focused on the aquaglyceroporin Fps1 and at the systems level we investigated the High Osmolarity Glycerol (HOG) pathway. Although Fps1 plays a key role in osmotic regulation and homeostasis, the mechanisms controlling Fps1 are not yet fully understood. We present evidence that Hog1 restricts the flux of glycerol and arsenite through Fps1 by phosphorylation of a residue within the N-terminal regulatory domain. This is the first report of a Mitogen Activated Protein Kinase (MAPK) regulating an aquaglyceroporin. In addition, we demonstrate that yet another MAPK, Slt2 may also be involved in regulating Fps1. It appears that Slt2 controls Fps1 by stimulating Fps1-mediated efflux. A residue within the C-terminal regulatory domain seems to be involved in controlling arsenite efflux through Fps1. Moreover, we show that in addition to the N- and C- termini, the transmembrane core of the protein also has a large effect on the transport activity of Fps1. Taken together, we speculate that phosphorylation of the termini affects the orientation of the transmembrane helices, thereby disturbing the transport activity of the protein. At the systems level we challenged the yeast HOG signal transduction pathway with systematic perturbation in the expression levels of its components under various external conditions to identify fragile nodes. We observed a high frequency of fragile nodes within the HOG pathway due to the inherent nature of signal transduction and the distribution of these fragile nodes was independent of function or location in the pathway topology. Moreover, the fragility patterns were mainly independent of the overall pathway activation status in response to different stresses. We found that the toxicity upon overexpression is at least partly due to pathway hyperactivation and can be suppressed by deletion of upstream or downstream pathway components. Furthermore, in silico analysis highlighted the impact of model structure on in silico robustness, and suggested complex formation and scaffolding as important contributors to the observed fragility patterns. Collectively, we believe that the robustness analysis can provide complementary information to dynamic data improving understanding of the operation of cellular signaling networks.sv
dc.language.isoengsv
dc.relation.haspartPaper I: The MAPK Hog1p Modulates Fps1p-dependent Arsenite Uptake and Tolerance in Yeast ::PMID::16885417sv
dc.relation.haspartPaper II: The MAP kinase Slt2 modulates transport through the aquaglyceroporin Fps1sv
dc.relation.haspartPaper III: Yeast aquaglyceroporins use the transmembrane core to restrict glycerol transportsv
dc.relation.haspartPaper IV: Robustness and fragility in the yeast high osmolarity glycerol (HOG) signal-transduction pathway ::PMID::19536204sv
dc.titleStress, Homeostasis and Robustness: Molecular and Systems Level Analysis in Yeastsv
dc.typeText
dc.type.svepDoctoral thesiseng
dc.gup.maildoryaneh.ahmadpour@cmb.gu.sesv
dc.type.degreeDoctor of Philosophysv
dc.gup.originGöteborgs universitet. Naturvetenskapliga fakultetensv
dc.gup.departmentDepartment of Cell and Molecular Biology ; Institutionen för cell- och molekylärbiologisv
dc.gup.defenceplaceTorsdagen den 24 Maj 2012, kl. 10.00, Hörsal Ragnar Sandberg, Medicinaregatan 7sv
dc.gup.defencedate2012-05-24
dc.gup.dissdb-fakultetMNF


Filer under denna titel

Thumbnail
Thumbnail

Dokumentet tillhör följande samling(ar)

Visa enkel post