Membrane curvature enables N-Ras lipid anchor sorting to liquid-ordered membrane phases


Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane curvature was essential for enrichment in raft-like liquid-ordered phases; enrichment was driven by relief of lateral pressure upon anchor insertion and most likely affects the localization of lipidated proteins in general.

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Figure 1: Membrane curvature enables the association of tN-Ras and palmitoyl anchors with lo membrane phases.
Figure 2: Increased relief of the lateral pressure in curved lo versus ld membranes as the underlying mechanism for preferential lo partitioning of lipidated moieties in highly curved membranes.


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This work was supported by the Lundbeck Foundation Center for Biomembranes in Nanomedicine, the Danish Councils for Independent and Strategic Research and the University of Copenhagen programs of excellence, 'Single-Molecule Nanoscience', 'BioScaRT' and 'UNIK-Synthetic Biology'. I.S. would like to acknowledge support from the U.S. National Science Foundation under grant no. CBET-1403058, and M.J.U acknowledges support from the US National Institutes of Health under grant no. P20GM103499.

Author information




D.S. conceived the strategy and was responsible for the overall project management. D.S., N.S.H., J.B.L. and M.B.J designed all experiments, which were performed by J.B.L. and M.B.J with help from N.S.H. and V.K.B. S.L.P. and K.J.J. synthesized and purified tN-Ras. M.J.U. and I.S. performed theoretical calculations of anchor partitioning. J.B.L., D.S., L.I. and N.S.H. wrote the manuscript. D.S. and N.S.H. supervised the project. All authors discussed the results and commented on the manuscript at all stages.

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Correspondence to Dimitrios Stamou.

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The authors declare no competing financial interests.

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Larsen, J., Jensen, M., Bhatia, V. et al. Membrane curvature enables N-Ras lipid anchor sorting to liquid-ordered membrane phases. Nat Chem Biol 11, 192–194 (2015).

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