Teo Wei Xuan, Kerr Markus Charles, Huston Wilhelmina May, Teasdale Rohan David
Institute for Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4067, Australia.
School of Life Sciences, University of Technology Sydney, Broadway, New South Wales 2007, Australia.
Biol Open. 2016 Apr 15;5(4):429-35. doi: 10.1242/bio.016485.
Chlamydia species are obligate intracellular pathogens that have a major impact on human health. The pathogen replicates within an intracellular niche called an inclusion and is thought to rely heavily on host-derived proteins and lipids, including ceramide. Sortilin is a transmembrane receptor implicated in the trafficking of acid sphingomyelinase, which is responsible for catalysing the breakdown of sphingomyelin to ceramide. In this study, we examined the role of sortilin in Chlamydia trachomatis L2 development. Western immunoblotting and immunocytochemistry analysis revealed that endogenous sortilin is not only associated with the inclusion, but that protein levels increase in infected cells. RNAi-mediated depletion of sortilin, however, had no detectable impact on ceramide delivery to the inclusion or the production of infectious progeny. This study demonstrates that whilst Chlamydia redirects sortilin trafficking to the chlamydial inclusion, RNAi knockdown of sortilin expression is insufficient to determine if this pathway is requisite for the development of the pathogen.
衣原体属是专性细胞内病原体,对人类健康有重大影响。该病原体在一种称为包涵体的细胞内龛中复制,并且被认为严重依赖宿主来源的蛋白质和脂质,包括神经酰胺。分拣蛋白是一种跨膜受体,与酸性鞘磷脂酶的运输有关,酸性鞘磷脂酶负责催化鞘磷脂分解为神经酰胺。在本研究中,我们研究了分拣蛋白在沙眼衣原体L2发育中的作用。蛋白质免疫印迹和免疫细胞化学分析显示,内源性分拣蛋白不仅与包涵体相关,而且在感染细胞中蛋白质水平升高。然而,RNA干扰介导的分拣蛋白缺失对神经酰胺向包涵体的递送或感染性子代的产生没有可检测到的影响。这项研究表明,虽然衣原体将分拣蛋白运输重定向至衣原体包涵体,但RNA干扰敲低分拣蛋白表达不足以确定该途径是否是病原体发育所必需的。