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Science 317 (5840): 947-951

Copyright © 2007 by the American Association for the Advancement of Science

Spatial Regulation of an E3 Ubiquitin Ligase Directs Selective Synapse Elimination

Mei Ding,1 Dan Chao,1,2 George Wang,1 Kang Shen1,2*

Abstract: Stereotyped synaptic connectivity can arise both by precise recognition between appropriate partners during synaptogenesis and by selective synapse elimination. The molecular mechanisms that underlie selective synapse removal are largely unknown. We found that stereotyped developmental elimination of synapses in the Caenorhabditis elegans hermaphrodite-specific motor neuron (HSNL) was mediated by an E3 ubiquitin ligase, a Skp1–cullin–F-box (SCF) complex composed of SKR-1 and the F-box protein SEL-10. SYG-1, a synaptic adhesion molecule, bound to SKR-1 and inhibited assembly of the SCF complex, thereby protecting nearby synapses. Thus, subcellular regulation of ubiquitin-mediated protein degradation contributes to precise synaptic connectivity through selective synapse elimination.

1 Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
2 Neuroscience Program, Stanford University, Stanford, CA 94305, USA.

* To whom correspondence should be addressed. E-mail: kangshen{at}

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