SNX9 activities are regulated by multiple phosphoinositides through both PX and BAR domains

Defne Yarar, Mark C. Surka, Marilyn C. Leonard, Sandra L. Schmid

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Sorting nexin 9 (SNX9) functions at the interface between membrane remodeling and the actin cytoskeleton. In particular, SNX9 links membrane binding to potentiation of N-WASP and dynamin GTPase activities. SNX9 is one of a growing number of proteins that contain two lipid-binding domains, a phox homology (PX) and a Bin1/Amphiphysin/ RVS167 (BAR) domain, and localizes to diverse membranes that are enriched in different phosphoinositides. Here, we investigate the mechanism by which SNX9 functions at these varied membrane environments. We show that SNX9 has low-lipid-binding affinity and harnesses a broad range of phosphoinositides to synergistically enhance both dynamin and N-WASP activities. We introduced point mutations in either the PX domain, BAR domain or both that are predicted to disrupt their functions and examined their respective roles in lipid-binding, and dynamin and N-WASP activation. We show that the broad lipid specificity of SNX9 is not because of independent and additive contributions by individual domains. Rather, the two domains appear to function in concert to confer lipid-binding and SNX9's membrane active properties. We also demonstrate that the two domains are differentially required for full SNX9 activity in N-WASP and dynamin regulation, and for localization of SNX9 to clathrin-coated pits and dorsal ruffles. In total, our results suggest that SNX9 can integrate signals from varied lipids through two domains to direct membrane remodeling events at multiple cellular locations.

Original languageEnglish (US)
Pages (from-to)133-146
Number of pages14
JournalTraffic
Volume9
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Actin
  • Dynamin
  • Membrane
  • N-WASP
  • Sorting nexin

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'SNX9 activities are regulated by multiple phosphoinositides through both PX and BAR domains'. Together they form a unique fingerprint.

  • Cite this