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Mol Brain. 2015 Jan 9;8:1. doi: 10.1186/s13041-014-0092-8.

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

Author information

1
Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, PO Box 9101, Nijmegen, 6500, HB, The Netherlands. mirthe.erkens@gmail.com.
2
Center for Functional Connectomics, Korea Institute of Science and Technology, 39-1 Hawolgokdong, Seongbukgu, Seoul, 136-791, Republic of Korea. keiko@kist.re.kr.
3
Laboratory of Electrophysiology, Université de Mons, Mons, 7000, Belgium. gcheron@ulb.ac.be.
4
Laboratory of Neurophysiology and Movement Biomechanics, CP601, ULB Neurosciences Institut, Université Libre de Bruxelles, Brussels, 1070, Belgium. gcheron@ulb.ac.be.
5
División de Neurociencias, Universidad Pablo de Olavide, Sevilla, 41013, Spain. jmarquez@upo.es.
6
Department of Cognitive Neurosciences, Nijmegen, 6500, HB, The Netherlands. jmarquez@upo.es.
7
Laboratory of Electrophysiology, Université de Mons, Mons, 7000, Belgium. cynthia.Prigogine@ulb.ac.be.
8
Laboratory of Neurophysiology and Movement Biomechanics, CP601, ULB Neurosciences Institut, Université Libre de Bruxelles, Brussels, 1070, Belgium. cynthia.Prigogine@ulb.ac.be.
9
Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, PO Box 9101, Nijmegen, 6500, HB, The Netherlands. j.schepens@ncmls.ru.nl.
10
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, PO Box 9101, Nijmegen, HB, 6500, The Netherlands. n.nadif@donders.ru.nl.
11
Center for Functional Connectomics, Korea Institute of Science and Technology, 39-1 Hawolgokdong, Seongbukgu, Seoul, 136-791, Republic of Korea. George.Augustine@ntu.edu.sg.
12
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. George.Augustine@ntu.edu.sg.
13
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore. George.Augustine@ntu.edu.sg.
14
Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, PO Box 9101, Nijmegen, 6500, HB, The Netherlands. w.hendriks@ncmls.ru.nl.

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.

PMID:
25571783
PMCID:
PMC4304614
DOI:
10.1186/s13041-014-0092-8
[Indexed for MEDLINE]
Free PMC Article

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