Filamentous actin regulates insulin exocytosis through direct interaction with Syntaxin 4

J Biol Chem. 2008 Apr 18;283(16):10716-26. doi: 10.1074/jbc.M709876200. Epub 2008 Feb 19.


Glucose-induced insulin exocytosis is coupled to associations between F-actin and SNARE proteins, although the nature and function of these interactions remains unknown. Toward this end we show here that both Syntaxin 1A and Syntaxin 4 associated with F-actin in MIN6 cells and that each interaction was rapidly and transiently diminished by stimulation of cells with d-glucose. Of the two isoforms, only Syntaxin 4 was capable of interacting directly with F-actin in an in vitro sedimentation assay, conferred by the N-terminal 39-112 residues of Syntaxin 4. The 39-112 fragment was capable of selective competitive inhibitory action, disrupting endogenous F-actin-Syntaxin 4 binding in MIN6 cells. Disruption of F-actin-Syntaxin 4 binding correlated with enhanced glucose-stimulated insulin secretion, mediated by increased granule accumulation at the plasma membrane and increased Syntaxin 4 accessibility under basal conditions. However, no increase in basal level Syntaxin 4-VAMP2 association occurred with either latrunculin treatment or expression of the 39-112 fragment. Taken together, these data disclose a new underlying mechanism by which F-actin negatively regulates exocytosis via binding and blocking Syntaxin 4 accessibility, but they also reveal the existence of additional signals and/or steps required to trigger the subsequent docking and fusion steps of exocytosis.

Publication types

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

MeSH terms

  • Actins / metabolism*
  • Amino Acid Motifs
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cell Line
  • Cell Membrane / metabolism
  • Exocytosis
  • Humans
  • Insulin / metabolism*
  • Mice
  • Models, Biological
  • Protein Binding
  • Protein Isoforms
  • Qa-SNARE Proteins / metabolism*
  • Rabbits
  • Thiazolidines / pharmacology


  • Actins
  • Bridged Bicyclo Compounds, Heterocyclic
  • Insulin
  • Protein Isoforms
  • Qa-SNARE Proteins
  • Thiazolidines
  • latrunculin B