From the ‡Istituto Superiore di Sanità, Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate.
§Istituto Superiore di Sanità, Dipartimento di Biologia Cellulare e Neuroscienze.
Mol Cell Proteomics. 2017 Oct;16(10):1801-1814. doi: 10.1074/mcp.M117.067041. Epub 2017 Aug 10.
Membrane microdomains that include lipid rafts, are involved in key physiological and pathological processes and participate in the entry of endocellular pathogens. These assemblies, enriched in cholesterol and sphingolipids, form highly dynamic, liquid-ordered phases that can be separated from the bulk membranes thanks to their resistance to solubilization by nonionic detergents. To characterize complexity and dynamics of detergent-resistant membranes of sexual stages of the rodent malaria parasite , here we propose an integrated study of raft components based on proteomics, lipid analysis and bioinformatics. This analysis revealed unexpected heterogeneity and unexplored pathways associated with these specialized assemblies. Protein-protein relationships and protein-lipid co-occurrence were described through multi-component networks. The proposed approach can be widely applied to virtually every cell type in different contexts and perturbations, under physiological and/or pathological conditions.
包含脂筏的膜微区参与关键的生理和病理过程,并参与细胞内病原体的进入。这些富含胆固醇和鞘脂的组装体形成高度动态的、有序的液相,可以通过它们对非离子去污剂的抗溶解能力与大部分膜分离。为了表征啮齿动物疟原虫有性阶段去污剂抗性膜的复杂性和动态性,我们在这里提出了一种基于蛋白质组学、脂质分析和生物信息学的筏成分综合研究。这项分析揭示了与这些特殊组装体相关的出乎意料的异质性和未探索的途径。通过多成分网络描述了蛋白质-蛋白质关系和蛋白质-脂质共现。所提出的方法可以广泛应用于不同生理和/或病理条件下不同环境和干扰下的几乎每一种细胞类型。