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The Anaphase-Promoting Complex Regulates the Abundance of GLR-1 Glutamate Receptors in the Ventral Nerve Cord of C. elegans

2004; Elsevier BV; Volume: 14; Issue: 22 Linguagem: Inglês

10.1016/j.cub.2004.11.010

1879-0445

Peter Juo, Joshua M. Kaplan,

Photoreceptor and optogenetics research

Abstract The anaphase-promoting complex (APC) is a multisubunit E3 ubiquitin ligase that targets key cell cycle regulatory proteins for degradation. Blockade of APC activity causes mitotic arrest [1, 2]. Recent evidence suggests that the APC may have roles outside the cell cycle [3–6]. Several studies indicate that ubiquitin plays an important role in regulating synaptic strength [7–13]. We previously showed that ubiquitin is directly conjugated to GLR-1, a C. elegans non-NMDA ( N -methyl-D-aspartate) class glutamate receptor (GluR), resulting in its removal from synapses [13]. By contrast, endocytosis of rodent AMPA GluRs is apparently regulated by ubiquitination of associated scaffolding proteins [12, 14]. Relatively little is known about the E3 ligases that mediate these effects. We examined the effects of perturbing APC function on postmitotic neurons in the nematode C. elegans . Temperature-sensitive mutations in APC subunits increased the abundance of GLR-1 in the ventral nerve cord. Mutations that block clathrin-mediated endocytosis blocked the effects of the APC mutations, suggesting that the APC regulates some aspect of GLR-1 recycling. Overexpression of ubiquitin decreased the density of GLR-1-containing synapses, and APC mutations blunted this effect. APC mutants had locomotion defects consistent with increased synaptic strength. This study defines a novel function for the APC in postmitotic neurons.