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p11 and its role in depression and therapeutic responses to antidepressants

Abstract

Studies of the multifunctional protein p11 (also known as S100A10) are shedding light on the molecular and cellular mechanisms underlying depression. Here, we review data implicating p11 in both the amplification of serotonergic signalling and the regulation of gene transcription. We summarize studies demonstrating that levels of p11 are regulated in depression and by antidepressant regimens and, conversely, that p11 regulates depression-like behaviours and/or responses to antidepressants. Current and future studies of p11 may provide a molecular and cellular framework for the development of novel antidepressant therapies.

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Figure 1: p11 expression in brain areas relevant to depression and antidepressant responses.
Figure 2: Pathways by which p11 mediates behavioural responses to antidepressants.
Figure 3: Protein structures of p11 and p11-binding proteins.
Figure 4: How SSRI antidepressants may regulate interactions between 5-HT receptors, p11, annexin A2 and SMARCA3.

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Acknowledgements

We acknowledge the important contributions of N. Heintz, E. Schmidt, D. Patel, P. Gao and M. Kaplitt to our understanding of the various functions of p11. This work was supported by the Fisher Center for Alzheimer's Research Foundation (P.S. and P.G.), W81XWH-09-1-0402 (P.G.), NIH MH090963 (P.G.), NIDA1RC2DA028968 (P.G.), The JPB Foundation (P.G.), W81XWH-09-1-0392 (Y.K.), W81XWH-09-1-0401 (J.L.W.-S.), and Swedish Research Council (P.S.). We apologize to the authors of the many interesting studies that could not be included owing to space constraints.

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Correspondence to Paul Greengard.

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Svenningsson, P., Kim, Y., Warner-Schmidt, J. et al. p11 and its role in depression and therapeutic responses to antidepressants. Nat Rev Neurosci 14, 673–680 (2013). https://doi.org/10.1038/nrn3564

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