CYTOSKELETAL ASSOCIATION IS IMPORTANT FOR DIFFERENTIAL TARGETING OF GLUCOSE-TRANSPORTER ISOFORMS IN LEISHMANIA

The major glucose transporter of the parasitic protozoan Leishmania en riettii exists in two isoforms, one of which (iso-1) localizes to the flagellar membrane, while the other (iso-2) localizes to the plasma me mbrane of the cell body, the pellicular membrane. These two isoforms d iffer only in their cytosolic NH2-terminal domains. Using immunoblots and immunofluorescence microscopy of detergent-extracted cytoskeletons , we have demonstrated that iso-2 associates with the microtubular cyt oskeleton that underlies the cell body membrane, whereas the flagellar membrane isoform iso-1 does not associate with the cytoskeleton. Dele tion mutants that remove the first 25 or more amino acids from iso-1 a re retargeted from the flagellum to the pellicular membrane, suggestin g that these deletions remove a signal required for flagellar targetin g. Unlike the full-length iso-1 protein, these deletion mutants associ ate with the cytoskeleton. Our results suggest that cytoskeletal bindi ng serves as an anchor to localize the iso-2 transporter within the pe llicular membrane, and that the flagellar targeting signal of iso-1 di verts this transporter into the flagellar membrane and away from the p ellicular microtubules.