Membrane targeting of the small myristoylated protein 2 (SMP-2) in Leishmania major

Leishmania parasites express three highly conserved small myristoylated proteins (SMPs) that are tar-geted to distinct membranes. SMP-1 is exclusively found in the flagellum, depending on myristoylationand palmitoylation. In contrast, monoacylated SMP-2 and SMP-4 are localized to the flagellar pocket andplasma membrane, respectively. Here, we demonstrate that unlike SMP-4, SMP-2 resides in detergentresistant membranes, but can be readily solubilized in the presence of high concentrations of salt. Weprovide evidence that in detergent resistant membranes, SMP-2 forms high molecular weight complexesin vivo. Association with detergent resistant membranes was abrogated in the presence of a C-terminal tagsuggesting acylation independent targeting signals. In addition, the N-terminal region of SMP-2 containssufficient information for membrane targeting, as a GFP-chimera localizes to the flagellar pocket. Thuswhile the core sequences of the SMPs are highly conserved, individual members have evolved differentmechanisms for their diverse membrane localization.Crown