Flagellar targeting and sensory function of a glucose transporter in L. mexicana.

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DESCRIPTION (provided by applicant): Leishmaniasis, trypanosomiasis, and malaria are parasitic diseases that affect more than 500 million individuals worldwide and are major public health problems (Teixeira et al., 2006; Wellems et al., 2009; WHO, 2010). Understanding the basic biology of these parasites is critical for developing methods to control disease. In these pathogenic organisms, a variety of membrane proteins are targeted to the flagellum, where they may serve in sensing the environment (Singla and Reiter, 2006; Bloodgood, 2010). While several proteins that are preferentially targeted to the flagellar membrane have been identified in Leishmania and the related trypanosomes (Piper et al., 1995; Godsel and Engman, 1999; Gull, 2003), how these proteins are targeted to the flagellum and what functions they perform on this sensory organ remain active areas of research. The three Leishmania mexicana glucose transporters offer an ideal system to investigate protein targeting to the flagellar membrane, as only the LmxGT1 isoform is targeted to the flagellum while the LmxGT2/LmxGT3 isoforms are localized to the plasma membrane of the cell body. The specific aims of this application are to: 1) identify the underlying mechanism that target LmxGT1 to the flagellar membrane, and 2) investigate a potential sensory function for this flagellar glucose transporter by examining the regulation of glucose uptake and chemotaxis behaviors of wild-type and lmxgt1 null-mutants. These studies aim to elucidate a flagellar targeting pathway that likely operates for multiple membrane proteins in Leishmania and related trypanosomes, as well as identify a flagellar specific sensory role for this glucose transporter.