Spatial regulation of an E3 ubiquitin ligase directs selective synapse elimination.
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.
Ding
Mei
M
Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
Chao
Dan
D
Wang
George
G
Shen
Kang
K
D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008959:Models, Neurological; D009046:Motor Neurons / Q000502:physiology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010058:Oviposition; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D050683:R-SNARE Proteins / Q000378:metabolism; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D020798:Two-Hybrid System Techniques
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D007136:Immunoglobulins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D011993:Recombinant Fusion Proteins; C109554:SEL-10 protein, C elegans; C473474:SYG-1 protein, C elegans; D044843:SKP Cullin F-Box Protein Ligases; C522506:SKR-1 protein, C elegans; D046988:Proteasome Endopeptidase Complex