Functional dissection of SYG-1 and SYG-2, cell adhesion molecules required for selective synaptogenesis in C. elegans.
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.
Chao
Daniel L
DL
Department of Biology and Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
Shen
Kang
K
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D007136:Immunoglobulins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D013329:Structure-Activity Relationship; D013569:Synapses / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D007136:Immunoglobulins; D009419:Nerve Tissue Proteins; C473474:SYG-1 protein, C elegans; C484036:SYG-2 protein, C elegans