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.

Mutations in the ligand-binding and pore domains control exit of glutamate receptors from the endoplasmic reticulum in C. elegans.

The abundance of ion channels and neurotransmitter receptors in the plasma membrane is limited by the efficiency of protein folding and subunit assembly in the endoplasmic reticulum (ER). The ER has a quality-control system for monitoring nascent proteins, which prevents incompletely folded and assembled proteins from being transported from the ER. Chaperone proteins identify unfolded and misassembled proteins in the ER via retention motifs that are normally buried at intersubunit contacts or via carbohydrate residues that are attached to misfolded domains.

Ubiquitin and AP180 regulate the abundance of GLR-1 glutamate receptors at postsynaptic elements in C. elegans.

Regulated delivery and removal of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors (GluRs) from postsynaptic elements has been proposed as a mechanism for regulating synaptic strength. Here we test the role of ubiquitin in regulating synapses that contain a C. elegans GluR, GLR-1.