Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/88520
Title: Protein tyrosine phosphatase receptor type R is required for Purkinje cell responsiveness in cerebellar long-term depression
Authors: Schepens, Jan TG
Kasri, Nael Nadif
Augustine, George James
Hendriks, Wiljan JAJ
Erkens, Mirthe
Tanaka-Yamamoto, Keiko
Cheron, Guy
Márquez-Ruiz, Javier
Prigogine, Cynthia
Keywords: Cerebellum
Long-term Synaptic Plasticity
DRNTU::Science::Medicine
Issue Date: 2015
Source: Erkens, M., Tanaka-Yamamoto, K., Cheron, G., Márquez-Ruiz, J., Prigogine, C., Schepens, . . . Hendriks, W. JAJ. (2015). Protein tyrosine phosphatase receptor type R is required for Purkinje cell responsiveness in cerebellar long-term depression. Molecular Brain, 8, 1-. doi:10.1186/s13041-014-0092-8
Series/Report no.: Molecular Brain
Abstract: 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.
URI: https://hdl.handle.net/10356/88520
http://hdl.handle.net/10220/45847
DOI: 10.1186/s13041-014-0092-8
Rights: © 2015 Erkens et al.; licensee BioMed Central. 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.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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