Freely turning over palmitate in erythrocyte membrane proteins is not responsible for the anchoring of lipid rafts to the spectrin skeleton: A study with bio-orthogonal chemical probes

► In erythrocytes, lipid rafts are anchored to the spectrin skeleton in a carbonate-sensitive manner. ► The palmitoylated protein p55 could contribute to this anchoring via its palmitate. ► p55 palmitoylation was studied with an ω-alkynyl analogue of palmitic acid and click chemistry. ► Carbonate does not depalmitoylate p55 but releases lipid rafts from membrane-skeleton. ► 2-bromopalmitate and cerulenin inhibit p55 palmitoylation without affecting lipid raft anchoring.