Plasma Membrane is the primary structure for adjusting to ever changing conditions. PM sub-compartmentalization in domains is thought to orchestrate signaling. Yet, mechanisms governing membrane organization are mostly uncharacterized. The plant-specific REMORINs are proteins regulating hormonal crosstalk and host invasion. REMs are the best-characterized nanodomain markers via an uncharacterized moiety called REMORIN C-terminal Anchor. By coupling biophysical methods, super-resolution microscopy and physiology, we decipher an original mechanism regulating the dynamic and organization of nanodomains. We showed that targeting of REMORIN is independent of the COP-II-dependent secretory pathway and mediated by PI4P and sterol. REM-CA is an unconventional lipid-binding motif that confers nanodomain organization. Analyses of REM-CA mutants by single particle tracking demonstrate that mobility and supramolecular organization are critical for immunity. This study provides a unique mechanistic insight into how the tight control of spatial segregation is critical in the definition of PM domain necessary to support biological function.DOI: http://dx.doi.org/10.7554/eLife.26404.001

Plasma membranes are complex entities common to all living cells. The basic principle of their organization appears very simple, but they are actually of high complexity and represent very dynamic structures. The interactions between bioactive molecules and lipids are important for numerous processes, from drug bioavailability to viral fusion. The cell membrane is a carefully balanced environment and any change inflicted upon its structure by a bioactive molecule must be considered in conjunction with the overall effect that this may have on the function and integrity of the membrane. Conceptually, understanding the molecular mechanisms by which bioactive molecules interact with cell membranes is of fundamental importance. Lipid specificity is a key factor for the detailed understanding of the penetration and/or activity of lipid-interacting molecules and of mechanisms of some diseases. Further investigation in that way should improve drug discovery and development of membrane-active molecules in many domains such as health, plant protection or microbiology. In this review, we will present complementary biophysical approaches that can give information about lipid specificity at a molecular point of view. Examples of application will be given for different molecule types, from biomolecules to pharmacological drugs. A special emphasis is given to cyclic lipopeptides since they are interesting molecules in the scope of this review by combining a peptidic moiety and a lipidic tail and by exerting their activity via specific interactions with the plasma membrane.

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