PhD defence Jannik Larsen – Københavns Universitet

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PhD defence Jannik Larsen

Membrane Curvature Regulates the Membrane Binding and Sorting of Ras

 Abstract:

Cellular organelles can be easily recognized based on the shape of their highly curved membranes. Recently, functionality was assigned to membrane shape, when it was shown that high membrane curvature can selectively recruit lipidated proteins. The regulation of this recruitment has been studied, mainly focusing on the properties of the lipid anchoring motif. Accordingly, how recruitment by membrane curvature is regulated by membrane and lipid properties, such as membrane packing order and lipid shape factors, has received little attention. Here we address this fundamental question by employing a single liposome curvature (SLiC) assay. Using confocal microscopy the SLiC assay allow us to quantify the curvature dependent binding of protein anchoring domains to immobilized liposomes of various sizes. Our main protein model system is the lipidated minimum anchoring motif of the signaling GTPase N-Ras (tN-Ras).

We find that not only protein features, but also membrane and lipid properties, such as membrane packing order, lipid shape and curvature shape, regulate the membrane curvature driven spatial localization of lipidated proteins, such as Ras. We propose that these different modes of regulation potentially combine in a synergistic manner in vivo to facilitate the tight spatial control necessary for cellular function.

 

Supervisor:

Prof. Dimitrios Stamou, Department of Chemistry, University of Copenhagen, Denmark

Assessment committee:

Prof. Birgitte Holst, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark

Prof. Luis A. Bagatolli, MEMPHYS – Center for Biomembrane Physics, University of Southern Denmark, Denmark

Prof. Patricia Bassereau, Institut Curie, Centre National de la Recherche Scientifique, France