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dc.contributor.authorPalmgren, Madelene
dc.date.accessioned2013-01-11T09:16:52Z
dc.date.available2013-01-11T09:16:52Z
dc.date.issued2013-01-11
dc.identifier.isbn978-91-628-8607-3
dc.identifier.urihttp://hdl.handle.net/2077/31506
dc.description.abstractAquaporins are found in all kingdoms of life where they are involved in water homeostasis. They are small transmembrane water conducting channels that belong to the ancient protein family Major Intrinsic Proteins (MIP). Early on in the evolution, a gene duplication event took place that divided the aquaporin family into two subgroups; orthodox aquaporins, which are strict water facilitators, and aquaglyceroporins that except for water also transport small uncharged solutes. The main questions that I have tried to address in this thesis are which regulatory mechanisms that are involved in aquaporin gating and to investigate transport differences in solute permeation. Specifically, we have investigated yeast and human aquaporins. To find answers to our questions, we have attempted to combine structural knowledge with functional analysis. A high resolution structure of P. pastoris orthodox Aqy1 to 1.15Å generated new knowledge of regulatory mechanisms and functions of the long N-terminus that is common among fungi. We suggest that Aqy1 is gated by phosphorylation and by mechanosensation. An important functional role of Aqy1 in rapid freeze thaw cycles could be demonstrated. During this work, a single deletion strain was generated that now serves as the primary aquaporin expression platform in our laboratory. Fps1 is a regulated glycerol facilitator that is important for yeast osmo-regulation. The regulatory mechanism is still not known but here we show that a suppressor mutation within the transmembrane region restrict glycerol by its transmembrane core. Thereby, we suggest that post translational modifications in the regulatory domains of N- and C-termini fine tunes glycerol flux through Fps1. The aquaglyceroporins are classified as having a dual transport function, namely being capable of facilitating the movement of both water and glycerol over the plasma membrane. In this study, we can clearly show that there are major differences in the substrate specificity and efficiency between the different aquaglyceroporins and that small changes affect the transport efficiency and specificity of the channels.sv
dc.language.isoengsv
dc.relation.haspartI.Fischer G, Kosinska-Eriksson U, Aponte-Santamaría C, Palmgren M, Geijer C, Hedfalk K, Hohmann S, de Groot BL, Neutze R, Lindkvist-Petersson K. Crystal structure of a yeast aquaporin at 1.15 angstrom reveals a novel gating mechanism. (2009) PLoS Biology Jun;7(6):e1000130.::PMID::19529756sv
dc.relation.haspartII. Geijer C*, Ahmadpour D*, Palmgren M, Filipsson C, Medrala-Klein D, Tamas M, Hohmann S, Lindkvist-Petersson K. * contributed equally Yeast aquaglyceroporins use the transmembrane core to control glycerol transport. J Biol Chem. 2012 Jul 6;287(28):23562-70.::PMID::22593571sv
dc.relation.haspartIII. Palmgren M, Geijer C, Eriksson S, Lasic S, Dahl P, Elbing K, Topgaard D, Lindkvist-Petersson K. Differences in transport efficiency and specificity of aquaglyceroporins explain novel roles in human health and disease Submitted to J Biol Chem. 2012 Decsv
dc.relation.haspartPaper IV Overexpression and characterization of human aquaglyceroporins AQP3 & AQP7 Kosinska-Eriksson U*, Palmgren M*, Elbing K, Lindkvist-Petersson K. * contributed equally Unpublished worksv
dc.subjectAquaporinsv
dc.subjectMembrane proteinsv
dc.subjectTransportsv
dc.subjectGlycerolsv
dc.subjectAquaglyceroporinssv
dc.subjectRegulationsv
dc.subjectarsenitesv
dc.titleRegulation and transport mechanisms of eukaryotic aquaporinssv
dc.typeTextswe
dc.type.svepDoctoral thesiseng
dc.gup.mailmadelene.palmgren@cmb.gu.sesv
dc.gup.mailmadelene.palmgren@gmail.comsv
dc.type.degreeDoctor of Philosophysv
dc.gup.originUniversity of Gothenburg. Faculty of Sciencesv
dc.gup.departmentDepartment of Cell and Molecular Biology ; Institutionen för cell- och molekylärbiologisv
dc.gup.defenceplaceFredagen den 1 februari 2013, kl. 9.30, Hörsal Arvid Carlsson, Academicum, Medicinaregatan 3sv
dc.gup.defencedate2013-02-01
dc.gup.dissdb-fakultetMNF


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