Annexin A2-dependent polymerization of actin mediates endosome biogenesis

Dev Cell. 2009 Mar;16(3):445-57. doi: 10.1016/j.devcel.2009.01.007.

Abstract

Early endosomes give rise to multivesicular intermediates during transport toward late endosomes. Much progress has been made in understanding the sorting of receptors into these intermediates, but the mechanisms responsible for their biogenesis remain unclear. Here, we report that F-actin is necessary for transport beyond early endosomes and endosome formation. We found that endosomes captured by actin cables were essentially stationary, but early endosomes also exhibited patches of F-actin and facilitated selective F-actin nucleation and polymerization. Our data show that nucleation of actin patches by early endosomes is strictly dependent on annexin A2, a protein involved in early-to-late endosome transport. It also requires the actin nucleation factor Spire1 and involves Arp2/3, which is needed for filament branching. We conclude that actin patches are nucleated on early endosomes via annexin A2 and Spire1, and that these patches control endosome biogenesis, presumably by driving the membrane remodeling process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / chemistry
  • Actins / metabolism*
  • Animals
  • Annexin A2 / antagonists & inhibitors
  • Annexin A2 / genetics
  • Annexin A2 / metabolism*
  • Base Sequence
  • Biological Transport, Active
  • Cell Line
  • Cricetinae
  • DNA Primers / genetics
  • Endosomes / metabolism*
  • Endosomes / ultrastructure
  • HeLa Cells
  • Humans
  • Microscopy, Electron, Transmission
  • RNA, Small Interfering / genetics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transfection

Substances

  • ANXA2 protein, human
  • Actin-Related Protein 2-3 Complex
  • Actins
  • Annexin A2
  • DNA Primers
  • RNA, Small Interfering
  • Recombinant Proteins