Connexin channels and phospholipids: association and modulation

摘要: For membrane proteins, lipids provide a structural framework and means to modulate function. Paired connexin hemichannels form the intercellular channels that compose gap junction plaques while unpaired have regulated functions in non-junctional plasma membrane. The importance of interactions between phospholipids is poorly understood. Endogenous most tightly associated with purified connexin26 or connexin32 junctional cell membranes, those likely and/or modulatory effects, were identified by tandem electrospray ionization-mass spectrometry using class-specific interpretative methods. Phospholipids characterized headgroup class, charge, glycerol-alkyl chain linkage acyl length saturation. results indicate specific endogenous are uniquely either channels, some both. Functional effects major phospholipid classes on channel activity assessed molecular permeability reconstituted into liposomes. Changes composition(s) liposome altered manner reflecting changes surface charge/potential and, secondarily, cholesterol content. Together, data show preference for tight association unique anionic phospholipids, these, independent headgroup, positive effect both channels. Additionally, suggest vivo modulators structure-function isoform-specific found cytoplasmic leaflet. A role promote negative curvature also inferred. This study first identify (endogenous) associate finding different isoforms suggests connexin-specific regulatory lipid membranes. interpreted light function biology, as informed current knowledge lipid-protein biophysics. intimate involvement distinct connexins contributes structure function, well plaque integrity, modulation lipophilic agents.