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

First Author  Oh YS Year  2013
Journal  Cell Volume  152
Issue  4 Pages  831-43
PubMed ID  23415230 Mgi Jnum  J:193813
Mgi Id  MGI:5469743 Doi  10.1016/j.cell.2013.01.014
Citation  Oh YS, et al. (2013) SMARCA3, a Chromatin-Remodeling Factor, Is Required for p11-Dependent Antidepressant Action. Cell 152(4):831-43
abstractText  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:
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