Dynamic interaction of HIV-1 Nef with the clathrin-mediated endocytic pathway at the plasma membrane

Anne Burtey, Joshua Z. Rappoport, Jérôme Bouchet, Stéphane Basmaciogullari, John Guatelli, Sanford M. Simon, Serge Benichou, Alexandre Benmerah*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


The HIV-1 Nef protein perturbs the trafficking of membrane proteins such as CD4 by interacting with clathrin-adaptor complexes. We previously reported that Nef alters early/recycling endosomes, but its role at the plasma membrane is poorly documented. Here, we used total internal reflection fluorescence microscopy, which restricts the analysis to a ∼100 nm region of the adherent surface of the cells, to focus on the dynamic of Nef at the plasma membrane relative to that of clathrin. Nef colocalized both with clathrin spots (CS) that remained static at the cell surface, corresponding to clathrin-coated pits (CCPs), and with ∼50% of CS that disappeared from the cell surface, corresponding to forming clathrin-coated vesicles (CCVs). The colocalization of Nef with clathrin required the di-leucine motif essential for Nef binding to AP complexes and was independent of CD4 expression. Furthermore, analysis of Nef mutants showed that the capacity of Nef to induce internalization and downregulation of CD4 in T lymphocytes correlated with its localization into CCPs. In conclusion, this analysis shows that Nef is recruited into CCPs and into forming CCVs at the plasma membrane, in agreement with a model in which Nef uses the clathrin-mediated endocytic pathway to induce internalization of some membrane proteins from the surface of HIV-1-infected T cells.

Original languageEnglish (US)
Pages (from-to)61-76
Number of pages16
Issue number1
StatePublished - Jan 2007


  • Clathrin
  • Endocytosis
  • HIV-1
  • Live cell imaging
  • Nef

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Structural Biology
  • Biochemistry
  • Cell Biology


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