Research article summary (published 13 May 2003):

Evidence for protein tyrosine phosphatase, tyrosine kinase, and G-protein regulation of the parallel fiber metabotropic slow EPSC of rat cerebellar Purkinje neurons.

Full Abstract

The slow EPSP (sEPSP) or slow EPSC (sEPSC) at parallel fiber to Purkinje neuron synapses is attributable to a nonselective cation channel coupled to activation of metabotropic type 1 glutamate receptors (mGluR1s). Photorelease of L-glutamate in 1 msec from 4-methoxy-7-nitroindolinyl-or 7-nitroindolinyl-caged glutamate in cerebellar slices was used to isolate and study postsynaptic mechanisms coupling mGluR1 to the cation channel. L-Glutamate immediately activated a glutamate transporter current, followed by the slow mGluR1-activated conductance. Inhibitors of kinases, phosphatases, and G-proteins were tested on the peak glutamate-evoked currents. No effects of the inhibitors were seen on the initial glutamate transporter currents. In contrast, the later mGluR1 currents were either unaffected or enhanced by the protein tyrosine kinase (PTK) inhibitors PP1, K252a, and staurosporine were diminished or blocked by phosphatase inhibitors but were unaffected by inhibitors of serine-threonine kinases PKA, PKC, or PKG. The selective src-PTK inhibitor PP1 (10 microm intracellularly) potentiated submaximal mGluR1 currents evoked by low L-glutamate concentrations but had no effect on maximal responses (80 or 160 microm L-glutamate). L-Glutamate-evoked mGluR1 currents and parallel fiber sEPSCs were reversibly and completely inhibited by protein tyrosine phosphatase (PTP) inhibitor bpV(phen) (50-200 microm) and by nonselective phosphatase inhibitor orthovanadate (0.5 or 1 mm). mGluR1 currents were completely inhibited by GDPbetaS applied intracellularly (5 mm). The results confirm a role for a GTPase postsynaptically, show that tyrosine phosphorylation inhibits mGluR1 coupling to the channel, and show that PTPs increase activation by tyrosine dephosphorylation most likely upstream of the sEPSP cation channel.

Author information

Author/s: Canepari, Marco (M); Ogden, David (D);

Affiliation: National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom.

Journal and publication information

Publication Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2003-May; vol 23 (issue 10) : pp 4066-71

Dates: Created 2003/05/23; Completed 2003/06/25; Revised 2007/11/15;

PMID: 12764093, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Cerebellum - drug effects; enzymology; physiology Enzyme Inhibitors - pharmacology Excitatory Postsynaptic Potentials - drug effects; physiology GTP-Binding Proteins - antagonists & inhibitors; physiology Nerve Fibers - drug effects; enzymology; physiology Phosphorylation - drug effects Presynaptic Terminals - drug effects; enzymology; physiology Protein Kinase C - antagonists & inhibitors

Protein Tyrosine Phosphatase, Non-Receptor Type 1 Protein Tyrosine Phosphatases - antagonists & inhibitors; physiology Protein-Tyrosine Kinases - antagonists & inhibitors; physiology Purkinje Cells - drug effects; enzymology; physiology Rats Rats, Wistar Receptors, Metabotropic Glutamate - metabolism; physiology Synaptic Transmission - drug effects; physiology Tyrosine - metabolism

Associated Chemicals: Enzyme Inhibitors (0) ; Receptors, Metabotropic Glutamate (0) ; Tyrosine (55520-40-6) ; Protein-Tyrosine Kinases (EC 2.7.1.112) ; Protein Kinase C (EC 2.7.11.13) ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 (EC 3.1.3.48) ; Protein Tyrosine Phosphatases (EC 3.1.3.48) ; GTP-Binding Proteins (EC 3.6.1.-)

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