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eNeuro. 2017 Feb 20;4(1). pii: ENEURO.0212-16.2017. doi: 10.1523/ENEURO.0212-16.2017. eCollection 2017 Jan-Feb.

The Kinase Function of MSK1 Regulates BDNF Signaling to CREB and Basal Synaptic Transmission, But Is Not Required for Hippocampal Long-Term Potentiation or Spatial Memory.

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Centre for Cognitive and Neural Systems, The University of Edinburgh , Edinburgh EH8 9JZ, United Kingdom.
MRC Protein Phosphorylation Unit, College of Life Sciences, The University of Dundee , Dundee DD1 5EH, United Kingdom.
School of Life Sciences, The University of Warwick , Coventry CV4 7AL, United Kingdom.
Division of Cell Signalling and Immunology, College of Life Sciences, The University of Dundee , Dundee DD1 5EH, United Kingdom.


The later stages of long-term potentiation (LTP) in vitro and spatial memory in vivo are believed to depend upon gene transcription. Accordingly, considerable attempts have been made to identify both the mechanisms by which transcription is regulated and indeed the gene products themselves. Previous studies have shown that deletion of one regulator of transcription, the mitogen- and stress-activated kinase 1 (MSK1), causes an impairment of spatial memory. Given the ability of MSK1 to regulate gene expression via the phosphorylation of cAMP response element binding protein (CREB) at serine 133 (S133), MSK1 is a plausible candidate as a prime regulator of transcription underpinning synaptic plasticity and learning and memory. Indeed, prior work has revealed the necessity for MSK1 in homeostatic and experience-dependent synaptic plasticity. However, using a knock-in kinase-dead mouse mutant of MSK1, the current study demonstrates that, while the kinase function of MSK1 is important in regulating the phosphorylation of CREB at S133 and basal synaptic transmission in hippocampal area CA1, it is not required for metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD), two forms of LTP or several forms of spatial learning in the watermaze. These data indicate that other functions of MSK1, such as a structural role for the whole enzyme, may explain previous observations of a role for MSK1 in learning and memory.


BDNF; CREB; LTP; MSK1; learning; memory

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