Regulation of tyrosine phosphatase STEP61 by protein kinase A during motor skill learning in mice
Authors: Laure Chagniel
Yan Bergeron
Michel Cyr
Guy Massicotte
Geneviève Bureau
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: STEP; PKA; motor skill learning; phosphorylation; hippocampus
Affiliations: Groupe de recherche en Neurosciences, Département de biologie médicale, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada.

Abstract:  Recently, striatal-enriched protein tyrosine phosphatase (STEP) and its upstream regulator protein kinase A (PKA) have been suspected to play a role in the intracellular mechanisms of fear conditioning and spatial memory. However, whether they contribute to the learning and memory of motor skills is totally unknown. In this study, we have investigated the role of STEP and PKA activities during motor skill learning associated with the accelerating rotarod task. We observed that learning the rotarod task differentially modulated the levels of phosphorylated STEP61 at serine 221, a site directly regulated by PKA, in the hippocampus, motor cortex and striatum. In a second set of experiments, we have pharmacologically inhibited PKA by the injection of Rp-cAMPS directly into the dorsal striatum of mice before rotarod trainings. PKA phosphorylation of STEP prevents the dephosphorylation of STEP substrates, whereas inhibition of PKA promotes STEP activity. Striatal PKA inhibitions dose-dependently impaired mice performances on the accelerating rotarod task. General motor abilities testing revealed an intact motor control in mice treated with 5 and 20 µg of Rp-cAMPS, but not at the highest dose of 40 µg. This suggested that motor learning was selectively affected by PKA inhibition at lower doses. Most notably, striatal inhibition of PKA reduced the levels of phosphorylated STEP61 at serine 221. Our data support that inactivation of STEP61 by the PKA activity is part of the molecular process associated with motor skill learning. 

Retracted: No

PubPeer comments:
 Five PubMed-indexed editorials with the same 3 authors published simultaneously. None of them cites the other, nor indicates that the same editorial was published simultaneously in 5 different journals. Norman K. Fry, Helina Marshall, Tasha Mellins-Cohen (2019) In praise of preprints. Microb Genom. 5(4). doi: 10.1099 mgen.0.000259; PMID: 30938670 Norman K. Fry, Helina Marshall, Tasha Mellins-Cohen (2019) In praise of preprints. Microbiology 165(5):489-491. doi: 10.1099 mic.0.000785; PMID: 30938669 Norman K. Fry, Helina Marshall, Tasha Mellins-Cohen (2019) In praise of preprints. Int J Syst Evol Microbiol, 69(7):1841-1843. doi: 10.1099 ijsem.0.003323; PMID: 30938668 Norman K. Fry, Helina Marshall, Tasha Mellins-Cohen (2019) In praise of preprints. J Med Microbiol, 68(4):503-505. doi: 10.1099 jmm.0.000954; PMID: 30938663 Norman K. Fry, Helina Marshall, Tasha Mellins-Cohen (2019) In praise of preprints. J Gen Virol, 100(5):733-735. doi: 10.1099 jgv.0.001239; PMID: 30938662 Notes: 1. In all 5 editorials: u201cAuthor contributions T.u2009M-C. prepared the initial draft. N.u2009K.u2009F. developed the manuscript in consultation with H.u2009M. and T.u2009M-C. All authors commented on and agreed the final version.u201d 2. In all 5 editorials: u201cConflicts of interest N. K. F. is Co-Editor in Chief for the Journal of Medical Microbiology, a Microbiology Society journal; H. M. is an Editor Mentee for Access Microbiology, a Microbiology Society journal; T. M-C is Director of Publishing for the Microbiology Society. The authors declare no other conflicts of interest.u201d 3. u201cThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.u201d This only appears in the Microb Genom. paper. 4. Four of the 5 editorials state u201cu00a9 2019 The Authorsu201d while the IJSEM editorial states u201cu00a9 2019 IUMSu201d. , 
 #1 Thank you for the flag. The editorial was co-published across the Microbiology Society s portfolio of journals, and we will have a note to that effect added on all items immediately. ,