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

描述(申请人提供)：利什曼病、锥虫病和疟疾是影响全球5亿多人的寄生虫病，是主要的公共卫生问题(Teixeira等人，2006年；Wellems等人，2009年；世卫组织，2010年)。了解这些寄生虫的基本生物学对于开发控制疾病的方法至关重要。在这些病原体中，各种膜蛋白被定位于鞭毛，在那里它们可能起到感知环境的作用(Singla和Reiter，2006；BroudGood，2010)。虽然在利什曼原虫和相关的锥虫中已经确定了几种优先定位于鞭毛膜的蛋白质(Piper等人，1995年；Godsel和Engman，1999；Gull，2003)，但这些蛋白质如何定位于鞭毛以及它们在这个感觉器官上执行的功能仍然是活跃的研究领域。墨西哥利什曼原虫的三种葡萄糖转运蛋白为研究定位于鞭毛膜的蛋白质提供了一个理想的系统，因为只有LmxGT1亚型定位于鞭毛，而LmxGT2/LmxGT3亚型定位于细胞体的质膜。本应用的具体目的是：1)确定将LmxGT1靶向鞭毛膜的潜在机制，以及2)通过检测野生型和lmxgt1缺失突变体对葡萄糖摄取和趋化行为的调节，来研究这种鞭毛状葡萄糖转运蛋白的潜在感觉功能。这些研究旨在阐明在利什曼原虫和相关锥虫中可能对多种膜蛋白起作用的鞭毛靶向途径，以及确定这种葡萄糖转运蛋白在鞭毛上的特定感觉作用。

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.