Functional dissection of SYG-1 and SYG-2, cell adhesion molecules required for selective synaptogenesis in C. elegans

Mol Cell Neurosci. 2008 Oct;39(2):248-57. doi: 10.1016/j.mcn.2008.07.001. Epub 2008 Jul 11.

Abstract

Cell adhesion molecules of the Immunoglobulin superfamily (IgCAMs) play diverse functions during neural development. Previously, we have identified SYG-1/Neph1 and SYG-2/Nephrin, IgCAMs necessary for synaptic specificity in Caenorhabditis elegans. Here, we conduct an in vivo structure-function analysis of SYG-1 and SYG-2 to identify domains of SYG-1 and SYG-2 necessary for heterophilic binding as well as synaptic specificity. We find the first Ig domain of SYG-1 and the first 5 Ig domains of SYG-2 are necessary and sufficient for their binding in vivo, as well as for synapse formation. We also find the SYG-2 cytoplasmic domain is required for SYG-2 subcellular trafficking, while the intracellular region of SYG-1 is required for synaptic function at earlier developmental stages, but is dispensable for later stages. This study defines the domain requirements for SYG-1/SYG-2 heterophilic binding and suggests that unknown SYG-1 extracellular interactors may play a role in SYG-1-mediated synaptic specificity.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Adhesion
  • Immunoglobulins / analysis
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism
  • Immunoglobulins / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neurogenesis / genetics
  • Neurogenesis / physiology*
  • Protein Binding
  • Protein Structure, Tertiary / genetics
  • Sequence Deletion / genetics
  • Structure-Activity Relationship
  • Synapses / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Immunoglobulins
  • Nerve Tissue Proteins
  • SYG-1 protein, C elegans
  • SYG-2 protein, C elegans