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Trends Biochem Sci. 2019 May 3. pii: S0968-0004(19)30081-7. doi: 10.1016/j.tibs.2019.04.001. [Epub ahead of print]

Tools for Understanding Nanoscale Lipid Regulation of Ion Channels.

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Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.
Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA. Electronic address:


Anionic phospholipids are minor but prominent components of the plasma membrane that are necessary for ion channel function. Their persistence in bulk membranes, in particular phosphatidylinositol 4,5-bisphosphate (PIP2), initially suggested they act as channel cofactors. However, recent technologies have established an emerging system of nanoscale signaling to ion channels based on lipid compartmentalization (clustering), direct lipid binding, and local lipid dynamics that allow cells to harness lipid heterogeneity to gate ion channels. The new tools to study lipid binding are set to transform our view of the membrane and answer important questions surrounding ion channel-delimited processes such as mechanosensation.


cryo-electron microscopy; lipid rafts; mass spectrometry; signaling lipids; super-resolution imaging


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