The GTPase Rab3b/3c-positive Recycling Vesicles Are Involved in Cross-Presentation in Dendritic Cells

Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15801-6. doi: 10.1073/pnas.0905684106. Epub 2009 Aug 28.

Abstract

Antigen cross-presentation in dendritic cells is a complex intracellular membrane transport process, but the underlying molecular mechanisms remain to be thoroughly investigated. In this study, we examined the effect of siRNA-mediated knockdown of 57 Rab GTPases, the key regulators of membrane trafficking, on antigen cross-presentation. Twelve Rab GTPases were identified to be associated with antigen cross-presentation, and Rab3b/3c was indicated to be colocalized with MHC class I molecules at perinuclear tubular structure. Tracing with fluorescence protein-tagged beta(2)-microglobulin demonstrated that the MHC class I molecules were internalized from the plasma membrane to Rab3b/3c-positive compartments, which were also colocalized with the internalized transferrin. Moreover, depletion of Rab3b/3c strongly reduced the fast phase recycling rate of transferrin receptors. Furthermore, the Rab3b/3c-positive compartments were colocalized with a fraction of Rab27a at a juxtaposition of phagosomes. Together, these data demonstrate that Rab3b/3c-positive recycling vesicles are involved in and may constitute one of the recycling compartments in exogenous antigen cross-presentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / physiology*
  • Biological Transport, Active
  • Cell Line
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Dendritic Cells / ultrastructure
  • Endosomes / immunology
  • Endosomes / metabolism
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Mice
  • Microscopy, Confocal
  • RNA, Small Interfering / genetics
  • rab3 GTP-Binding Proteins / antagonists & inhibitors
  • rab3 GTP-Binding Proteins / genetics
  • rab3 GTP-Binding Proteins / metabolism*

Substances

  • Histocompatibility Antigens Class I
  • RNA, Small Interfering
  • RAB3B protein, human
  • RAB3C protein, human
  • Rab3b protein, mouse
  • Rab3c protein, mouse
  • rab3 GTP-Binding Proteins