title: 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.
abstract: The later stages of long-term potentiation (LTP)in vitroand spatial memoryin vivoare 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.
authors.affiliation: Centre for Cognitive and Neural Systems, The University of Edinburgh , Edinburgh EH8 9JZ, United Kingdom.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Daumas
authors.affiliation: MRC Protein Phosphorylation Unit, College of Life Sciences, The University of Dundee , Dundee DD1 5EH, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hunter
authors.affiliation: School of Life Sciences, The University of Warwick , Coventry CV4 7AL, United Kingdom.
authors.forename: Rajen B
authors.initials: RB
authors.lastname: Mistry
authors.affiliation: School of Life Sciences, The University of Warwick , Coventry CV4 7AL, United Kingdom.
authors.forename: Lorenzo
authors.identifier: 0000-0003-1156-2861
authors.initials: L
authors.lastname: Morè
authors.affiliation: School of Life Sciences, The University of Warwick , Coventry CV4 7AL, United Kingdom.
authors.forename: Lucia
authors.identifier: 0000-0002-3280-8026
authors.initials: L
authors.lastname: Privitera
authors.affiliation: School of Life Sciences, The University of Warwick , Coventry CV4 7AL, United Kingdom.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Cooper
authors.affiliation: Division of Cell Signalling and Immunology, College of Life Sciences, The University of Dundee , Dundee DD1 5EH, United Kingdom.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Reyskens
authors.affiliation: School of Life Sciences, The University of Warwick , Coventry CV4 7AL, United Kingdom.
authors.forename: Harry T
authors.initials: HT
authors.lastname: Flynn
authors.affiliation: Centre for Cognitive and Neural Systems, The University of Edinburgh , Edinburgh EH8 9JZ, United Kingdom.
authors.forename: Richard G M
authors.identifier: 0000-0001-8661-1520
authors.initials: RG
authors.lastname: Morris
authors.affiliation: Division of Cell Signalling and Immunology, College of Life Sciences, The University of Dundee , Dundee DD1 5EH, United Kingdom.
authors.forename: J Simon C
authors.identifier: 0000-0002-8135-1958
authors.initials: JS
authors.lastname: Arthur
authors.affiliation: School of Life Sciences, The University of Warwick , Coventry CV4 7AL, United Kingdom.
authors.forename: Bruno G
authors.identifier: 0000-0001-7214-3172
authors.initials: BG
authors.lastname: Frenguelli
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003463:Cues; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D012694:Serine; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1
keywords: BDNF; CREB; LTP; MSK1; learning; memory