The anaphase-promoting the abundance of GLR-1 complex regulates glutamate receptors in the ventral nerve cord of C-elegans

被引:137
作者
Juo, P [1 ]
Kaplan, JM [1 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA
关键词
D O I
10.1016/j.cub.2004.11.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2057 / 2062
页数:6
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