An SCF-like ubiquitin ligase complex that controls presynaptic differentiation

Nature. 2004 Jul 15;430(6997):345-50. doi: 10.1038/nature02647. Epub 2004 Jun 20.


During synapse formation, specialized subcellular structures develop at synaptic junctions in a tightly regulated fashion. Cross-signalling initiated by ephrins, Wnts and transforming growth factor-beta family members between presynaptic and postsynaptic termini are proposed to govern synapse formation. It is not well understood how multiple signals are integrated and regulated by developing synaptic termini to control synaptic differentiation. Here we report the identification of FSN-1, a novel F-box protein that is required in presynaptic neurons for the restriction and/or maturation of synapses in Caenorhabditis elegans. Many F-box proteins are target recognition subunits of SCF (Skp, Cullin, F-box) ubiquitin-ligase complexes. fsn-1 functions in the same pathway as rpm-1, a gene encoding a large protein with RING finger domains. FSN-1 physically associates with RPM-1 and the C. elegans homologues of SKP1 and Cullin to form a new type of SCF complex at presynaptic periactive zones. We provide evidence that T10H9.2, which encodes the C. elegans receptor tyrosine kinase ALK (anaplastic lymphoma kinase), may be a target or a downstream effector through which FSN-1 stabilizes synapse formation. This neuron-specific, SCF-like complex therefore provides a localized signal to attenuate presynaptic differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Animals
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Differentiation*
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism*
  • Gene Expression Regulation
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • Macromolecular Substances
  • Mutation / genetics
  • Neurons / cytology
  • Neurons / enzymology
  • Neurons / metabolism
  • Organ Specificity
  • Protein Binding
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases
  • SKP Cullin F-Box Protein Ligases / chemistry*
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Signal Transduction
  • Substrate Specificity
  • Synapses / enzymology*
  • Synapses / metabolism


  • Caenorhabditis elegans Proteins
  • F-Box Proteins
  • FSN-1 protein, C elegans
  • Guanine Nucleotide Exchange Factors
  • Macromolecular Substances
  • RPM-1 protein, C elegans
  • SKP Cullin F-Box Protein Ligases
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases