CELL AND DEVELOPMENTAL BIOLOGY OF TRYPANOSOMATID PARASITES

人类病原体利什曼原虫的细胞和发育生物学 相关的锥虫寄生虫作为Intra的模型被研究。 以及胞外寄生。重点放在描述 寄生虫独特表膜的基本功能和基因结构 酶和相关蛋白在确定它们在寄生虫中的作用 生存和发展。 杜氏乳杆菌3‘-核苷酸酶/核酸酶(e’-NT/Nu)基因的探针 被用来将该基因定位到一个2.5Mb大小的单一LD上 染色体也存在于其他各种致病病毒中 利什曼原虫。因此，该基因的基本结构是 在物种谱系中保存。营养素诱导的细胞因子过度表达 LD 3‘-NT/Nu酶活性受两者调节 转录介导的事件和翻译后修饰 新合成的蛋白质。在同源的上体中 转染-表达研究表明，LD表面膜3‘Nt/Nu 转化为并表达为具有酶活性的可溶性的 通过删除其跨膜锚定结构域来分泌蛋白质 吉恩。在其他研究中，该基因为唯一的LD表面膜酸 鉴定和鉴定了磷酸酶(MBACP)。一个MBACP 用基因探针将该基因定位在一个约1.45的基因上 MB大小的LD染色体，也存在于各种不同的 致病利什曼原虫的基本结构表明 基因也跨越了物种的界限而被保守。我们最近也是 鉴定了一种新的38 kDa膜核酸酶，该酶存在于两种蛋白质中 和无鞭毛虫。基于其表面局部化和本构关系 表达，我们假设这种酶一定在 寄生虫对宿主来源的核碱基的获取。最后，基因 对编码钙网蛋白利什曼同源物的基因进行了鉴定。它的 表达的蛋白具有多种功能，包括高钙离子 结合和自激酶活性，最重要的是， 同系物利什曼原的非磷酸化结合活性 RNA。后者提示钙网织蛋白可能在RNA中起作用。 在这些寄生虫中加工、运输或保护。

The cell and developmental biology of the human pathogen, Leishmania, and related trypanosomatid parasites are investigated as models of both intra and extracellular parasitism. Emphasis is placed on characterizing the basic functions and gene structure of unique parasite surface membrane enzymes and related proteins toward defining their roles in parasite survival and development. A probe from the L. donovani(Ld)3'-nucleotidase/nuclease (e'-NT/Nu) gene was used to map the locus of this gene to a single about 2.5 Mb sized Ld chromosome which was also present in a variety of other pathogenic Leishmania species. Thus, the basic structure of this gene has been conserved across species lines. The nutrient-induced over-expression of Ld 3'-NT/Nu enzyme activity ws shown to be regulated by both transcriptionally mediated events and posttranslational modification of the newly synthesized protein. In homologous episomal transfection-expression studies, the Ld surface membrane 3'NT/Nu was converted into, and expressed as, a soluble, enzymatically active secretory protein by deleting the transmembrane anchor domain from its gene. In other studies, the gene for the unique Ld surface membrane acid phosphatase (MbAcP) was identified and characterized. An MbAcP gene-probe was used to map the locus of this gene to a single about 1.45 Mb sized Ld chromosome which was also present in various different pathogenic Leishmania species indicating that the basic structure of this gene has also been conserved across species boundaries. We also recently identified a new 38 kDa surface membrane nuclease present in both Ld pro and amastigotes. Based on its surface localization and constitutive expression, we assume that this enzyme must play an essential role in parasite acquisition of host-derived nucleo-bases. Finally, the gene encoding the leishmanial homolog of calreticulin was characterized. Its expressed protein possessed multiple functions including both high Ca++ binding and autokinase activities and, most significantly, phosphorylation-independent binding activity for homologous leishmanial RNAs. The latter suggests that calreticulin may play a role in RNA processing, transport or protection in these parasites.