An Integrated Approach to Explore Composition and Dynamics of Cholesterol-rich Membrane Microdomains in Sexual Stages of Malaria Parasite

Mol Cell Proteomics. 2017 Oct;16(10):1801-1814. doi: 10.1074/mcp.M117.067041. Epub 2017 Aug 10.

Abstract

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 Plasmodium berghei, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholesterol / chemistry
  • Cholesterol / metabolism
  • Computer Simulation
  • Detergents / chemistry
  • Disease Models, Animal
  • Gametogenesis / physiology
  • Humans
  • Life Cycle Stages / physiology*
  • Lipids / analysis
  • Malaria / parasitology*
  • Membrane Microdomains / chemistry
  • Membrane Microdomains / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Plasmodium berghei / growth & development*
  • Plasmodium berghei / metabolism*
  • Proteomics
  • Sphingolipids / chemistry
  • Sphingolipids / metabolism

Substances

  • Detergents
  • Lipids
  • Sphingolipids
  • Cholesterol