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. 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.
Grunwald
Maria E
ME
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Mellem
Jerry E
JE
Strutz
Nathalie
N
Maricq
Andres V
AV
Kaplan
Joshua M
JM
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D002966:Clathrin / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000235:genetics* / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D015220:Calcium Channels; D002966:Clathrin; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D011994:Recombinant Proteins; D025801:Ubiquitin; C096470:glr-1 protein, C elegans; D018698:Glutamic Acid