Role of RBC membrane protein palmitoylation in regulation of molecular topology and susceptibility to Plasmodium falciparum invasion

Squeezability of biconcave RBC raises a fundamental query, about, how it can restructure its bendable cytoskeleton for efficient micro-circulation. We report for the first time, the existence of dynamic palmitoylome in RBC composed of 118 palmitoylated proteins that reduced to 42 upon treatment with 2BP, a generic inhibitor of palmitoylation. In-depth analysis revealed that Semaphorin7A, CR1 and ABCB6, the known RBC receptors for were reduced to negligible in 2BP-treated RBCs, suggesting palmitoylation-dependent recruitment of parasite-specific receptors. Interestingly, Kell, a single disulphide-linked co-partner in Kell-Kx complex was undetected in 2BP-treated RBCs, while Kx remained intact. RBCs-blocked with anti-Kell antibody demonstrated signficant reduction in parasite invasion, thus suggesting it as a receptor proto-type for invasion. Finally, reduced expression of Kell in palmitoylated protein pool of sickle-cell RBC ghost, with its diminished surface representation in these RBCs, proposed Kell, as one of the novel receptor-prototype for invasion.