Clathrin-Mediated Endocytosis Is Required for Compensatory Regulation of GLR-1 Glutamate Receptors after Activity Blockade

Chronic changes in neural activity trigger a variety of compensatory homeostatic mechanisms by which neurons maintain a normal level of synaptic input. Here we show that chronic activity blockade triggers a compensatory change in the abundance of GLR-1, a Caenorhabditis elegans glutamate receptor. I...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 101; no. 9; pp. 3190 - 3195
Main Authors Grunwald, Maria E., Mellem, Jerry E., Strutz, Nathalie, Maricq, Andres V., Kaplan, Joshua M., Goodman, Corey S.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 02.03.2004
National Acad Sciences
Subjects
AMPA receptors
Animals
Biological Sciences
Brain
Caenorhabditis elegans
Caenorhabditis elegans - physiology
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - physiology
Calcium Channels - physiology
Clathrin - physiology
clathrin adaptin protein
eat-4 gene
Endocytosis
Endocytosis - physiology
Fluorescence
Gene expression regulation
Gene Expression Regulation - physiology
Glutamic Acid - metabolism
Glutamic Acid - pharmacology
Models, Biological
Neurology
Neurons
Neuroscience
Patch-Clamp Techniques
Receptors
Receptors, AMPA
Receptors, Glutamate - genetics
Receptors, Glutamate - physiology
Recombinant Proteins - metabolism
Recycling
Synapses
Synapses - physiology
Ubiquitin - metabolism
unc-11 gene
Voltage dependent calcium channels
Worms
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Summary:Chronic changes in neural activity trigger a variety of compensatory homeostatic mechanisms by which neurons maintain a normal level of synaptic input. Here we show that chronic activity blockade triggers a compensatory change in the abundance of GLR-1, a Caenorhabditis elegans glutamate receptor. In mutants lacking a voltage-dependent calcium channel (unc-2) or a vesicular glutamate transporter (VGLUT; eat-4), the abundance of GLR-1 in the ventral nerve cord was increased. Similarly, the amplitude of glutamate-evoked currents in ventral cord interneurons was increased in eat-4 VGLUT mutants compared with wild-type controls. The effects of eat-4 VGLUT mutations on GLR-1 abundance in the ventral cord were eliminated in double mutants lacking both the clathrin adaptin protein unc-11 AP180 and eat-4 VGLUT. In contrast, mutations that decreased ubiquitination of GLR-1 did not prevent increased ventral cord abundance of GLR-1 in eat-4 VGLUT mutants. Taken together, our results suggest that GLR-1 is regulated in a homeostatic manner and that this effect depends on clathrin-mediated endocytosis but does not require ubiquitination of GLR-1.
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Abbreviations: GluR, glutamate receptor; VDCC, voltage-dependent calcium channel; VGLUT, vesicular glutamate transporter; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA, N-methyl-d-aspartate.
Present address: Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA 02129.
This paper was submitted directly (Track II) to the PNAS office.
To whom correspondence should be addressed at: Department of Molecular Biology, Massachusetts General Hospital, Wellman 8, 50 Blossom Street, Boston, MA 02114. E-mail: kaplan@molbio.mgh.harvard.edu.
Edited by Corey S. Goodman, Renovis, South San Francisco, CA, and approved January 9, 2004
Present address: Institute of Physiology I, University of Tübingen, Gmelinstrasse 5, D-72076 Tübingen, Germany.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0306156101