The Immunoglobulin Super Family Protein RIG-3 Prevents Synaptic Potentiation and Regulates Wnt Signaling

• Published in: Neuron (Cambridge, Mass.) Mass.), 2011-07, Vol.71 (1), p.103-116
• Main Authors: Babu, Kavita, Hu, Zhitao, Chien, Shih-Chieh, Garriga, Gian, Kaplan, Joshua M.
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors; Aldicarb - pharmacology; Amino acids; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins - antagonists & inhibitors; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Caenorhabditis elegans Proteins - physiology; Cell adhesion & migration; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - physiology; Defects; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - genetics; Excitatory Postsynaptic Potentials - physiology; Experiments; Genes; Membrane Proteins - genetics; Membrane Proteins - physiology; Motor Neurons - drug effects; Motor Neurons - metabolism; Motor Neurons - physiology; Mutation; Neuronal Plasticity - genetics; Neuronal Plasticity - physiology; Neurons; Proteins; Receptor Protein-Tyrosine Kinases - antagonists & inhibitors; Receptor Tyrosine Kinase-like Orphan Receptors; Receptors, Nicotinic - metabolism; Signal Transduction - genetics; Signal Transduction - physiology; Synaptic Transmission - physiology; Target recognition; Wnt Proteins - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2011.05.034

Cell surface Ig superfamily proteins (IgSF) have been implicated in several aspects of neuron development and function. Here, we describe the function of a  Caenorhabditis elegans IgSF protein, RIG-3. Mutants lacking RIG-3 have an exaggerated paralytic response to a cholinesterase inhibitor, aldicarb. Although RIG-3 is expressed in motor neurons, heightened drug responsiveness was caused by an aldicarb-induced increase in muscle ACR-16 acetylcholine receptor (AChR) abundance, and a corresponding potentiation of postsynaptic responses at neuromuscular junctions. Mutants lacking RIG-3 also had defects in the anteroposterior polarity of the ALM mechanosensory neurons. The effects of RIG-3 on synaptic transmission and ALM polarity were both mediated by changes in Wnt signaling, and in particular by inhibiting CAM-1, a Ror-type receptor tyrosine kinase that binds Wnt ligands. These results identify RIG-3 as a regulator of Wnt signaling, and suggest that RIG-3 has an anti-plasticity function that prevents activity-induced changes in postsynaptic receptor fields. ► Presynaptic RIG-3 inhibits activity-induced changes in postsynaptic responses ► Activity-induced delivery of ACR-16 nAChRs is enhanced in rig-3 mutants ► RIG-3 acts as an antiplasticity molecule ► RIG-3 regulates Wnt signaling