Possible role of deep tubular invaginations of the plasma membrane in MHC-I trafficking

Exp Cell Res. 2005 May 15;306(1):142-9. doi: 10.1016/j.yexcr.2005.01.021. Epub 2005 Mar 23.

Abstract

Tubules and vesicles are membrane carriers involved in traffic along the endocytic and secretory routes. The small GTPase Arf6 regulates a recycling branch of short dynamic tubular intermediates used by major histocompatibility class I (MHC-I) molecules to traffic through vesicles between endosomes and the plasma membrane. We observed that Arf6 also affects a second network of very long and stable tubules containing MHC-I, many of which correspond to deep invaginations of the plasma membrane. Treatment with wortmannin, an inhibitor of phosphatidylinositol-3-phosphate kinase, prevents formation of the short dynamic tubules while increasing the number of the long and very stable ones. Expression of NefAAAA, a mutant form of HIV Nef, increases the number of cells containing the stable tubules, and is used here as a tool to facilitate their study. Photoactivation of NefAAAA-PA-GFP demonstrates that this molecule traffics from endosomes to the tubules. Finally, live-cell imaging also shows internalization of MHC-I molecules into these tubules, suggesting that this is an additional route for MHC-I traffic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factor 6
  • ADP-Ribosylation Factors / genetics
  • Androstadienes / pharmacology
  • Cell Line, Tumor*
  • Cell Membrane Structures / drug effects
  • Cell Membrane Structures / physiology*
  • Cell Membrane Structures / ultrastructure
  • Cytoplasmic Vesicles / metabolism
  • Endocytosis / physiology
  • Endosomes / metabolism
  • Gene Products, nef / analysis
  • Gene Products, nef / genetics
  • Gene Products, nef / metabolism
  • Histocompatibility Antigens Class I / analysis
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Microscopy, Electron
  • Models, Biological
  • Mutation / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors / pharmacology
  • Protein Transport / physiology
  • Transduction, Genetic
  • Transfection
  • Wortmannin

Substances

  • ADP-Ribosylation Factor 6
  • Androstadienes
  • Gene Products, nef
  • Histocompatibility Antigens Class I
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • ADP-Ribosylation Factors
  • ARF6 protein, human
  • Wortmannin