Hierarchical assembly of presynaptic components in defined C. elegans synapses

Nat Neurosci. 2006 Dec;9(12):1488-98. doi: 10.1038/nn1806. Epub 2006 Nov 19.


The presynaptic regions of axons accumulate synaptic vesicles, active zone proteins and periactive zone proteins. However, the rules for orderly recruitment of presynaptic components are not well understood. We systematically examined molecular mechanisms of presynaptic development in egg-laying synapses of Caenorhabditis elegans, demonstrating that two scaffolding molecules, SYD-1 and SYD-2, have key roles in presynaptic assembly. SYD-2 (liprin-alpha) was previously shown to regulate the size and the shape of active zones. We now show that in syd-1 and syd-2 mutants, synaptic vesicles and numerous other presynaptic proteins fail to accumulate at presynaptic sites. SYD-1 and SYD-2 function cell-autonomously at presynaptic terminals, downstream of synaptic specificity molecule SYG-1. SYD-1 is likely to act upstream of SYD-2 to positively regulate its synaptic assembly activity. These data imply a hierarchical organization of presynaptic assembly, in which transmembrane specificity molecules initiate synaptogenesis by recruiting a few key scaffolding proteins, which in turn assemble other presynaptic components.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cytoskeleton / metabolism
  • Immunoglobulins / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Motor Neurons / metabolism
  • Mutation
  • Nerve Tissue Proteins / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Presynaptic Terminals / metabolism*


  • Caenorhabditis elegans Proteins
  • Immunoglobulins
  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • SYD-1 protein, C elegans
  • SYD-2 protein, C elegans
  • SYG-1 protein, C elegans
  • UNC-104 protein, C elegans