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
Authors
Mirthe Erkens게이코 야마모토Guy CheronJavier Marquez-RuizCynthia PrigogineJan TG SchepensNael Nadif KasriGeorge J AugustineWiljan JAJ Hendriks
Keywords
Cerebellum; ERK; Long-term synaptic plasticity; Knock-out mice; LTD; PTPBR7; PTP-SL
Issue Date
2015-01
Publisher
Molecular Brain
Citation
VOL 8, NO 1, 1-13
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
http://pubs.kist.re.kr/handle/201004/49355
ISSN
17566606
Appears in Collections:
KIST Publication > Article
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