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Protein tyrosine phosphatase receptor type R is required for Purkinje cell responsiveness in cerebellar long-term depression

BACKGROUND: Regulation of synaptic connectivity, including long-term depression (LTD), allows proper tuning of cellular signalling processes within brain circuitry. In the cerebellum, a key centre for motor coordination, a positive feedback loop that includes mitogen-activated protein kinases (MAPKs...

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Autores principales: Erkens, Mirthe, Tanaka-Yamamoto, Keiko, Cheron, Guy, Márquez-Ruiz, Javier, Prigogine, Cynthia, Schepens, Jan TG, Nadif Kasri, Nael, Augustine, George J, Hendriks, Wiljan JAJ
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304614/
https://www.ncbi.nlm.nih.gov/pubmed/25571783
http://dx.doi.org/10.1186/s13041-014-0092-8
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author Erkens, Mirthe
Tanaka-Yamamoto, Keiko
Cheron, Guy
Márquez-Ruiz, Javier
Prigogine, Cynthia
Schepens, Jan TG
Nadif Kasri, Nael
Augustine, George J
Hendriks, Wiljan JAJ
author_facet Erkens, Mirthe
Tanaka-Yamamoto, Keiko
Cheron, Guy
Márquez-Ruiz, Javier
Prigogine, Cynthia
Schepens, Jan TG
Nadif Kasri, Nael
Augustine, George J
Hendriks, Wiljan JAJ
author_sort Erkens, Mirthe
collection PubMed
description BACKGROUND: Regulation of synaptic connectivity, including long-term depression (LTD), allows proper tuning of cellular signalling processes within brain circuitry. In the cerebellum, a key centre for motor coordination, a positive feedback loop that includes mitogen-activated protein kinases (MAPKs) is required for proper temporal control of LTD at cerebellar Purkinje cell synapses. Here we report that the tyrosine-specific MAPK-phosphatase PTPRR plays a role in coordinating the activity of this regulatory loop. RESULTS: LTD in the cerebellum of Ptprr(−/−) mice is strongly impeded, in vitro and in vivo. Comparison of basal phospho-MAPK levels between wild-type and PTPRR deficient cerebellar slices revealed increased levels in mutants. This high basal phospho-MAPK level attenuated further increases in phospho-MAPK during chemical induction of LTD, essentially disrupting the positive feedback loop and preventing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) phosphorylation and endocytosis. CONCLUSIONS: Our findings indicate an important role for PTPRR in maintaining low basal MAPK activity in Purkinje cells. This creates an optimal ‘window’ to boost MAPK activity following signals that induce LTD, which can then propagate through feed-forward signals to cause AMPAR internalization and LTD.
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spelling pubmed-43046142015-01-24 Protein tyrosine phosphatase receptor type R is required for Purkinje cell responsiveness in cerebellar long-term depression Erkens, Mirthe Tanaka-Yamamoto, Keiko Cheron, Guy Márquez-Ruiz, Javier Prigogine, Cynthia Schepens, Jan TG Nadif Kasri, Nael Augustine, George J Hendriks, Wiljan JAJ Mol Brain Research BACKGROUND: Regulation of synaptic connectivity, including long-term depression (LTD), allows proper tuning of cellular signalling processes within brain circuitry. In the cerebellum, a key centre for motor coordination, a positive feedback loop that includes mitogen-activated protein kinases (MAPKs) is required for proper temporal control of LTD at cerebellar Purkinje cell synapses. Here we report that the tyrosine-specific MAPK-phosphatase PTPRR plays a role in coordinating the activity of this regulatory loop. RESULTS: LTD in the cerebellum of Ptprr(−/−) mice is strongly impeded, in vitro and in vivo. Comparison of basal phospho-MAPK levels between wild-type and PTPRR deficient cerebellar slices revealed increased levels in mutants. This high basal phospho-MAPK level attenuated further increases in phospho-MAPK during chemical induction of LTD, essentially disrupting the positive feedback loop and preventing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) phosphorylation and endocytosis. CONCLUSIONS: Our findings indicate an important role for PTPRR in maintaining low basal MAPK activity in Purkinje cells. This creates an optimal ‘window’ to boost MAPK activity following signals that induce LTD, which can then propagate through feed-forward signals to cause AMPAR internalization and LTD. BioMed Central 2015-01-09 /pmc/articles/PMC4304614/ /pubmed/25571783 http://dx.doi.org/10.1186/s13041-014-0092-8 Text en © Erkens et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Erkens, Mirthe
Tanaka-Yamamoto, Keiko
Cheron, Guy
Márquez-Ruiz, Javier
Prigogine, Cynthia
Schepens, Jan TG
Nadif Kasri, Nael
Augustine, George J
Hendriks, Wiljan JAJ
Protein tyrosine phosphatase receptor type R is required for Purkinje cell responsiveness in cerebellar long-term depression
title Protein tyrosine phosphatase receptor type R is required for Purkinje cell responsiveness in cerebellar long-term depression
title_full Protein tyrosine phosphatase receptor type R is required for Purkinje cell responsiveness in cerebellar long-term depression
title_fullStr Protein tyrosine phosphatase receptor type R is required for Purkinje cell responsiveness in cerebellar long-term depression
title_full_unstemmed Protein tyrosine phosphatase receptor type R is required for Purkinje cell responsiveness in cerebellar long-term depression
title_short Protein tyrosine phosphatase receptor type R is required for Purkinje cell responsiveness in cerebellar long-term depression
title_sort protein tyrosine phosphatase receptor type r is required for purkinje cell responsiveness in cerebellar long-term depression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304614/
https://www.ncbi.nlm.nih.gov/pubmed/25571783
http://dx.doi.org/10.1186/s13041-014-0092-8
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