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


Authors: Oh, Y. S.; Gao, P.; Lee, K. W.; Ceglia, I.; Seo, J. S.; Zhang, X.; Ahn, J. H.; Chait, B. T.; Patel, D. J.; Kim, Y.; Greengard, P.
Article Title: SMARCA3, a chromatin-remodeling factor, is required for p11-dependent antidepressant action
Abstract: 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: © 2013 Elsevier Inc.
Journal Title: Cell
Volume: 152
Issue: 4
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2013-02-14
Start Page: 831
End Page: 843
Language: English
DOI: 10.1016/j.cell.2013.01.014
PROVIDER: scopus
PUBMED: 23415230
PMCID: PMC3633087
DOI/URL:
Notes: --- - "Export Date: 1 March 2013" - "CODEN: CELLB" - "Source: Scopus"
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  1. Dinshaw J Patel
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  2. Pu Gao
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