Erkens, Mirthe Tanaka-Yamamoto, Keiko Cheron, Guy Marquez-Ruiz, Javier Prigogine, Cynthia Schepens, Jan T. G. Kasri, Nael Nadif Augustine, George J. Hendriks, Wiljan J. A. J. 2024-01-20T08:01:34Z 2024-01-20T08:01:34Z 2021-09-05 2015-01-09 1756-6606 https://pubs.kist.re.kr/handle/201004/125873 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 alpha-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. English BMC SIGNAL-REGULATED KINASE PTP-SL SYNAPTIC DEPRESSION MAP KINASE INOSITOL TRISPHOSPHATE ARACHIDONIC-ACID LATE-PHASE ACTIVATION PHOSPHORYLATION INDUCTION Protein tyrosine phosphatase receptor type R is required for Purkinje cell responsiveness in cerebellar long-term depression Article 10.1186/s13041-014-0092-8 1 MOLECULAR BRAIN, v.8 MOLECULAR BRAIN 8 scie scopus 000348233500001 Neurosciences Neurosciences & Neurology Article SIGNAL-REGULATED KINASE PTP-SL SYNAPTIC DEPRESSION MAP KINASE INOSITOL TRISPHOSPHATE ARACHIDONIC-ACID LATE-PHASE ACTIVATION PHOSPHORYLATION INDUCTION Cerebellum ERK Long-term synaptic plasticity Knock-out mice LTD PTPBR7 PTP-SL