Hernandez Yunuen, Castillo Cynthia, Roychowdhury Sukla, Hehl Adrian, Aley Stephen B, Das Siddhartha
Infectious Diseases/Immunology, University of Texas at El Paso, TX 79968-0519, USA.
Int J Parasitol. 2007 Jan;37(1):21-32. doi: 10.1016/j.ijpara.2006.09.008. Epub 2006 Oct 12.
Although identified as an early-diverged protozoan, Giardia lamblia shares many similarities with higher eukaryotic cells, including an internal membrane system and cytoskeleton, as well as secretory pathways. However, unlike many other eukaryotes, Giardia does not synthesize lipids de novo, but rather depends on exogenous sources for both energy production and organelle or membrane biogenesis. It is not known how lipid molecules are taken up by this parasite and if endocytic pathways are involved in this process. In this investigation, we tested the hypothesis that highly regulated and selective lipid transport machinery is present in Giardia and necessary for the efficient internalization and intracellular targeting of ceramide molecules, the major sphingolipid precursor. Using metabolic and pathway inhibitors, we demonstrate that ceramide is internalized through endocytic pathways and is primarily targeted into perinuclear/endoplasmic reticulum membranes. Further investigations suggested that Giardia uses both clathrin-dependent pathways and the actin cytoskeleton for ceramide uptake, as well as microtubule filaments for intracellular localization and targeting. We speculate that this parasitic protozoan has evolved cytoskeletal and clathrin-dependent endocytic mechanisms for importing ceramide molecules from the cell exterior for the synthesis of membranes and vesicles during growth and differentiation.
尽管贾第虫被鉴定为一种早期分化的原生动物，但它与高等真核细胞有许多相似之处，包括内膜系统、细胞骨架以及分泌途径。然而，与许多其他真核生物不同的是，贾第虫不会从头合成脂质，而是依赖外源来源进行能量产生以及细胞器或膜的生物合成。目前尚不清楚这种寄生虫如何摄取脂质分子，以及内吞途径是否参与这一过程。在本研究中，我们检验了这样一个假设：贾第虫中存在高度调控且具有选择性的脂质转运机制，这对于神经酰胺分子（主要的鞘脂前体）的有效内化和细胞内靶向是必需的。使用代谢和途径抑制剂，我们证明神经酰胺是通过内吞途径内化的，并且主要靶向到核周/内质网膜。进一步的研究表明，贾第虫利用网格蛋白依赖性途径和肌动蛋白细胞骨架摄取神经酰胺，还利用微管丝进行细胞内定位和靶向。我们推测，这种寄生原生动物已经进化出细胞骨架和网格蛋白依赖性内吞机制，用于从细胞外部导入神经酰胺分子，以在生长和分化过程中合成膜和囊泡。
