SMARCA3, a chromatin-remodeling factor, is required for p11-dependent antidepressant action

Cell. 2013 Feb 14;152(4):831-43. doi: 10.1016/j.cell.2013.01.014.


p11, through unknown mechanisms, is required for behavioral and cellular responses to selective serotonin reuptake inhibitors (SSRIs). We show that SMARCA3, a chromatin-remodeling factor, is a target for the p11/annexin A2 heterotetrameric complex. Determination of the crystal structure indicates that SMARCA3 peptide binds to a hydrophobic pocket in the heterotetramer. Formation of this complex increases the DNA-binding affinity of SMARCA3 and its localization to the nuclear matrix fraction. In the dentate gyrus, both p11 and SMARCA3 are highly enriched in hilar mossy cells and basket cells. The SSRI fluoxetine induces expression of p11 in both cell types and increases the amount of the ternary complex of p11/annexin A2/SMARCA3. SSRI-induced neurogenesis and behavioral responses are abolished by constitutive knockout of SMARCA3. Our studies indicate a central role for a chromatin-remodeling factor in the SSRI/p11 signaling pathway and suggest an approach to the development of improved antidepressant therapies. PAPERCLIP:

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Annexin A2 / metabolism*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Dentate Gyrus / metabolism*
  • Female
  • Male
  • Models, Molecular
  • Molecular Sequence Data
  • Mossy Fibers, Hippocampal / metabolism
  • S100 Proteins / metabolism*
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Sequence Alignment
  • Signal Transduction
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • X-Ray Diffraction


  • Annexin A2
  • DNA-Binding Proteins
  • S100 Proteins
  • S100 calcium binding protein A10
  • Serotonin Uptake Inhibitors
  • Smarca3 protein, mouse
  • Transcription Factors

Associated data

  • PDB/4HRE
  • PDB/4HRG
  • PDB/4HRH