Profilin II regulates the exocytosis of kainate glutamate receptors

J Biol Chem. 2010 Dec 17;285(51):40060-71. doi: 10.1074/jbc.M110.140442. Epub 2010 Oct 11.


The trafficking of ionotropic glutamate receptors to and from synaptic sites is regulated by proteins that interact with their cytoplasmic C-terminal domain. Profilin IIa (PfnIIa), an actin-binding protein expressed in the brain and recruited to synapses in an activity-dependent manner, was shown previously to interact with the C-terminal domain of the GluK2b subunit splice variant of kainate receptors (KARs). Here, we characterize this interaction and examine the role of PfnIIa in the regulation of KAR trafficking. PfnIIa directly and specifically binds to the C-terminal domain of GluK2b through a diproline motif. Expression of PfnIIa in transfected COS-7 cells and in cultured hippocampal neurons from PfnII-deficient mice decreases the level of extracellular of homomeric GluK2b as well as heteromeric GluK2a/GluK2b KARs. Our data suggest a novel mechanism by which PfnIIa exerts a dual role on the trafficking of KARs, by a generic inhibition of clathrin-mediated endocytosis through its interaction with dynamin-1, and by controlling KARs exocytosis through a direct and specific interaction with GluK2b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Clathrin / genetics
  • Clathrin / metabolism
  • Dynamin I / genetics
  • Dynamin I / metabolism
  • Exocytosis / physiology*
  • Gene Expression Regulation / physiology
  • GluK2 Kainate Receptor
  • Hippocampus / metabolism*
  • Mice
  • Mice, Knockout
  • Neurons / metabolism*
  • Profilins / genetics
  • Profilins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport / physiology
  • Receptors, Kainic Acid / genetics
  • Receptors, Kainic Acid / metabolism*
  • Synapses / genetics
  • Synapses / metabolism*


  • Clathrin
  • Profilins
  • Receptors, Kainic Acid
  • Dynamin I