Palmitoylation of MPP1 (membrane-palmitoylated protein 1)/p55 is crucial for lateral membrane organization in erythroid cells |
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Authors: | Łach Agnieszka Grzybek Michał Heger Elzbieta Korycka Justyna Wolny Marcin Kubiak Jakub Kolondra Adam Bogusławska Dzamila M Augoff Katarzyna Majkowski Michał Podkalicka Joanna Kaczor Jakub Stefanko Adam Kuliczkowski Kazimierz Sikorski Aleksander F |
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Institution: | Laboratory of Cytobiochemistry, Biotechnology Faculty, University of Wroc?aw, Przybyszewskiego 63/77, 51-148 Wroc?aw, Poland. |
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Abstract: | S-Acylation of proteins is a ubiquitous post-translational modification and a common signal for membrane association. The major palmitoylated protein in erythrocytes is MPP1, a member of the MAGUK family and an important component of the ternary complex that attaches the spectrin-based skeleton to the plasma membrane. Here we show that DHHC17 is the only acyltransferase present in red blood cells (RBC). Moreover, we give evidence that protein palmitoylation is essential for membrane organization and is crucial for proper RBC morphology, and that the effect is specific for MPP1. Our observations are based on the clinical cases of two related patients whose RBC had no palmitoylation activity, caused by a lack of DHHC17 in the membrane, which resulted in a strong decrease of the amount of detergent-resistant membrane (DRM) material. We confirmed that this loss of detergent-resistant membrane was due to the lack of palmitoylation by treatment of healthy RBC with 2-bromopalmitic acid (2-BrP, common palmitoylation inhibitor). Concomitantly, fluorescence lifetime imaging microscopy (FLIM) analyses of an order-sensing dye revealed a reduction of membrane order after chemical inhibition of palmitoylation in erythrocytes. These data point to a pathophysiological relationship between the loss of MPP1-directed palmitoylation activity and perturbed lateral membrane organization. |
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Keywords: | Lipid Raft Membrane Function Membrane Proteins Membrane Structure Protein Palmitoylation DHHC/ZDHHC MPP1(p55) Protein Palmitoylation Hemolytic Anemia Membrane Microdomains (Rafts) Red Blood Cell Membrane |
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