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      The Importance of Plasma Membrane Nanodomains in Signal Transduction and Drug Repurposing

      25-26 October 2023
      Cell topography, cholesterol, laurdan, lipid rafts, live cell imaging, membrane nanodomains, plasma membrane, signal transduction, statins, T cells


            The current dogma says that nanodomains of tightly packed lipids in the plasma membrane, also known as lipid rafts, of nanometre size in resting cells aggregate to become signalling hotspots upon T cell receptor (TCR) engagement. Intriguingly, we have shown that TCR engagement is not required for a T cell signalling response - it can also be invoked by temperature or lipid composition changes which are accompanied by the aggregation of signalling molecules in lipid rafts. We have also shown that molecular pinning of membrane molecules, i.e. their transient immobilisation, for instance when surface molecules are aggregated using antibodies, causes the formation of lipid rafts where the aggregation occurs. The TCR, we have found to be located in lipid raft both in resting and activated cells. Our results demonstrate that both the formation and coalescence of lipid rafts can result in a T cell signalling response by creating an environment where signalling molecules are highly concentrated, exceeding the threshold for a signalling response. Models of how the plasma membrane biophysical rearrangement could be linked to intracellular signalling and cell topography will be presented as will examples of how drug repurposing of statins to target the biophysical organisation of the plasma membrane can combat disease.


            Author and article information

            20 September 2023
            [1 ] Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg (Sweden) ( https://ror.org/01tm6cn81)
            Author information

            Published under Creative Commons Attribution 4.0 International ( CC BY 4.0). Users are allowed to share (copy and redistribute the material in any medium or format) and adapt (remix, transform, and build upon the material for any purpose, even commercially), as long as the authors and the publisher are explicitly identified and properly acknowledged as the original source.

            Stockholm, Sweden
            25-26 October 2023



            Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
            Pharmacology & Pharmaceutical medicine
            Cell topography,cholesterol,laurdan,lipid rafts,live cell imaging,membrane nanodomains,plasma membrane,signal transduction,statins,T cells


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