biostudies-literatureYang GSNational Institute of General Medical SciencesNIGMS NIH HHS2256-2270https://www.ebi.ac.uk/biostudies/studies/S-EPMC11331041biostudies-literatureUnknown123(15)Interleaflet coupling-the influence of one leaflet on the properties of the opposing leaflet-is a fundamental plasma membrane organizational principle. This coupling is proposed to participate in maintaining steady-state biophysical properties of the plasma membrane, which in turn regulates some transmembrane signaling processes. A prominent example is antigen (Ag) stimulation of signaling by clustering transmembrane receptors for immunoglobulin E (IgE), FcεRI. This transmembrane signaling depends on the stabilization of ordered regions in the inner leaflet for sorting of intracellular signaling components. The resting inner leaflet has a lipid composition that is generally less ordered than the outer leaflet and that does not spontaneously phase separate in model membranes. We propose thaBiophysical journalLipid-driven interleaflet coupling of plasma membrane order regulates FcεRI signaling in mast cells.PMC11331041R35GM122493R01GM117552R01 GM117552R35 GM122493Suresh PYang GSWagenknecht-Wiesner AYin BBaird BABag NLondon EfalseLipid-driven interleaflet coupling of plasma membrane order regulates FcεRI signaling in mast cells.Interleaflet coupling-the influence of one leaflet on the properties of the opposing leaflet-is a fundamental plasma membrane organizational principle. This coupling is proposed to participate in maintaining steady-state biophysical properties of the plasma membrane, which in turn regulates some transmembrane signaling processes. A prominent example is antigen (Ag) stimulation of signaling by clustering transmembrane receptors for immunoglobulin E (IgE), FcεRI. This transmembrane signaling depends on the stabilization of ordered regions in the inner leaflet for sorting of intracellular signaling components. The resting inner leaflet has a lipid composition that is generally less ordered than the outer leaflet and that does not spontaneously phase separate in model membranes. We propose tha2024-01-01T00:00:00Z2024 Aug2026-03-27T17:14:20.287Z2025-08-30T03:09:55.446ZS-EPMC113310413753325810.1016/j.bpj.2023.07.027