Dynamics of ESCRT protein recruitment during retroviral assembly

Nat Cell Biol. 2011 Apr;13(4):394-401. doi: 10.1038/ncb2207. Epub 2011 Mar 10.

Abstract

The ESCRT (endosomal sorting complex required for transport) complexes and associated proteins mediate membrane scission reactions, such as multivesicular body formation, the terminal stages of cytokinesis and retroviral particle release. These proteins are believed to be sequentially recruited to the site of membrane scission, and then complexes are disassembled by the ATPase Vps4A. However, these events have never been observed in living cells, and their dynamics are unknown. By quantifying the recruitment of several ESCRT and associated proteins during the assembly of two retroviruses, we show that Alix progressively accumulated at viral assembly sites, coincident with the accumulation of the main viral structural protein, Gag, and was not recycled after assembly. In contrast, ESCRT-III and Vps4A were transiently recruited only when the accumulation of Gag was complete. These data indicate that the rapid and transient recruitment of proteins that act late in the ESCRT pathway and carry out membrane fission is triggered by prior and progressive accumulation of proteins that bridge viral proteins and the late-acting ESCRT proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Membrane / metabolism
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Gene Products, gag / genetics
  • Gene Products, gag / metabolism
  • HIV-1 / physiology
  • HIV-1 / ultrastructure
  • HeLa Cells
  • Humans
  • Infectious Anemia Virus, Equine / physiology
  • Infectious Anemia Virus, Equine / ultrastructure
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Retroviridae / physiology*
  • Retroviridae / ultrastructure
  • Vacuolar Proton-Translocating ATPases / metabolism*
  • Virus Assembly*

Substances

  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Gene Products, gag
  • PDCD6IP protein, human
  • Recombinant Fusion Proteins
  • Vacuolar Proton-Translocating ATPases
  • ATPases Associated with Diverse Cellular Activities
  • VPS4A protein, human