Abstract
The metabotropic glutamate (mGlu) receptors are a family of receptors involved in the tuning of fast excitatory synaptic transmission in the brain. Experiments performed in heterologous expression systems suggest that cell surface expression of group I mGlu receptors is controlled by their auxiliary protein, Homer. However, whether or not this also applies to neurons remains controversial. Here we show that in cultured cerebellar granule cells, the group I mGlu receptor subtype, mGlu5, transfected alone is functionally expressed at the surface of these neurons. Transfected Homer1b caused intracellular retention and clustering of this receptor at synaptic sites. Recombinant Homer1a alone did not affect cell surface expression of the receptor, but in neurons transfected with Homer1b, excitation-induced expression of native Homer1a reversed the intracellular retention of mGlu5 receptors, resulting in the receptor trafficking to synaptic membranes. Transfected Homer1a also increased the latency and amplitude of the mGlu5 receptor Ca2+ response. These results indicate that Homer1 proteins regulate synaptic cycling and Ca2+ signaling of mGlu5 receptors, in response to neuronal activity.
(c) 2002 Elsevier Science (USA).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Membrane / drug effects
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Cell Membrane / metabolism*
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Cells, Cultured
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Cerebellum / cytology
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Cerebellum / metabolism
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Homer Scaffolding Proteins
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Membrane Potentials / drug effects
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Membrane Potentials / genetics
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Mice
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Neurites / drug effects
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Neurites / metabolism
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Neurites / ultrastructure
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Neuropeptides / genetics
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Neuropeptides / metabolism*
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Potassium Channels / drug effects
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Potassium Channels / metabolism
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Protein Isoforms / drug effects
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Transport / drug effects
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Protein Transport / physiology*
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Reaction Time / drug effects
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Reaction Time / physiology
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Receptor, Metabotropic Glutamate 5
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Receptors, Cell Surface / drug effects
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Receptors, Metabotropic Glutamate / drug effects
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Receptors, Metabotropic Glutamate / genetics
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Receptors, Metabotropic Glutamate / metabolism*
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Recombinant Fusion Proteins / drug effects
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Synaptic Membranes / drug effects
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Synaptic Membranes / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
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Transfection
Substances
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Carrier Proteins
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Homer Scaffolding Proteins
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Homer1 protein, mouse
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Neuropeptides
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Potassium Channels
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Protein Isoforms
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Receptor, Metabotropic Glutamate 5
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Receptors, Cell Surface
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Receptors, Metabotropic Glutamate
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Recombinant Fusion Proteins