SNX9 couples actin assembly to phosphoinositide signals and is required for membrane remodeling during endocytosis

Dev Cell. 2007 Jul;13(1):43-56. doi: 10.1016/j.devcel.2007.04.014.


Multiple modes of endocytosis require actin-dependent remodeling of the plasma membrane; however, neither the factors linking these processes nor their mechanisms of action are understood. The sorting nexin, SNX9, localizes to clathrin-coated pits where it interacts with dynamin and functions in clathrin-mediated endocytosis. Here, we demonstrate that SNX9 also localizes to actin-rich structures implicated in fluid-phase uptake, including tubular membranes containing GPI-anchored proteins and dorsal membrane ruffles. Moreover, we show that SNX9 is critical for dorsal ruffle formation and for clathrin-independent, actin-dependent fluid-phase endocytosis. In vitro, SNX9 directly associates with N-WASP, an Arp2/3 complex activator, and stimulates N-WASP/Arp2/3-mediated actin assembly. SNX9-stimulated actin polymerization is greatly enhanced by PI(4,5)P(2)-containing liposomes, due in part to PI(4,5)P(2)-induced SNX9 oligomerization. These results suggest a mechanism for the spatial and temporal regulation of N-WASP-dependent actin assembly and implicate SNX9 in directly coupling actin dynamics to membrane remodeling during multiple modes of endocytosis.

Publication types

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

MeSH terms

  • Actin-Related Protein 2 / metabolism
  • Actin-Related Protein 3 / metabolism
  • Actins / metabolism*
  • Animals
  • Cell Line
  • Dimerization
  • Endocytosis / physiology*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphatidylinositols / metabolism*
  • Protein Structure, Tertiary
  • Rabbits
  • Signal Transduction / physiology*
  • Sorting Nexins
  • Vesicular Transport Proteins / chemistry
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*
  • Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism
  • src Homology Domains / physiology


  • ACTR2 protein, human
  • ACTR3 protein, human
  • Actin-Related Protein 2
  • Actin-Related Protein 3
  • Actins
  • Membrane Proteins
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • SNX9 protein, human
  • Sorting Nexins
  • Vesicular Transport Proteins
  • Wiskott-Aldrich Syndrome Protein, Neuronal