Flotillin-1-enriched Lipid Raft Domains Accumulate on Maturing Phagosomes

Jean François Dermine, Sophie Duclos, Jérome Garin, François St.-Louis, Shane Rea, Robert G. Parton, Michel Desjardins

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Abstract

Flotillin-1 was recently shown to be enriched on detergent-resistant domains of the plasma membrane called lipid rafts. These rafts, enriched in sphingolipids and cholesterol, sequester certain proteins while excluding others. Lipid rafts have been implicated in numerous cellular processes including signal transduction, membrane trafficking, and molecular sorting. In this study, we demonstrate both morphologically and biochemically that lipid rafts are present on phagosomes. These structures are enriched in flotillin-1 and devoid of the main phagosomes membrane protein lysosomal-associated membrane protein (LAMP1). The flotillin-1 present on phagosomes does not originate from the plasma membrane during phagocytosis but accumulates gradually on maturing phagosomes. Treatment with bafilomycin A1, a compound that inhibits the proton pump ATPase and prevents the fusion of phagosomes with late endocytic organelles, prevents the acquisition of flotillin-1 by phagosomes, indicating that this protein might be recruited on phagosomes from endosomal organelles. A proteomic characterization of the lipid rafts of phagosomes indicates that actin, the α-and β-subunits of heterotrimeric G proteins, as well as subunits of the proton pump V-ATPase are among the constituents of these domains. Remarkably, the intracellular parasite Leishmania donovani can actively inhibit the acquisition of flotillin-1-enriched lipid rafts by phagosomes and the maturation of these organelles. These results indicate that specialized functions required for phagolysosome biogenesis may occur at focal points on the phagosome membrane, and therefore represent a potential target of intracellular pathogens.

Original languageEnglish (US)
Pages (from-to)18507-18512
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number21
DOIs
StatePublished - Jan 25 2001

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Dermine, J. F., Duclos, S., Garin, J., St.-Louis, F., Rea, S., Parton, R. G., & Desjardins, M. (2001). Flotillin-1-enriched Lipid Raft Domains Accumulate on Maturing Phagosomes. Journal of Biological Chemistry, 276(21), 18507-18512. https://doi.org/10.1074/jbc.M101113200