Wnt signaling regulates acetylcholine receptor translocation and synaptic plasticity in the adult nervous system
Department of Neurobiology; Francis Lab
Medical Subject Headings
Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Chromosome Pairing; Mutation; Nervous System; Neuromuscular Junction; Neuronal Plasticity; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Receptors, G-Protein-Coupled; Receptors, Nicotinic; Wnt Proteins; *Wnt Signaling Pathway
Neuroscience and Neurobiology
The adult nervous system is plastic, allowing us to learn, remember, and forget. Experience-dependent plasticity occurs at synapses--the specialized points of contact between neurons where signaling occurs. However, the mechanisms that regulate the strength of synaptic signaling are not well understood. Here, we define a Wnt-signaling pathway that modifies synaptic strength in the adult nervous system by regulating the translocation of one class of acetylcholine receptors (AChRs) to synapses. In Caenorhabditis elegans, we show that mutations in CWN-2 (Wnt ligand), LIN-17 (Frizzled), CAM-1 (Ror receptor tyrosine kinase), or the downstream effector DSH-1 (disheveled) result in similar subsynaptic accumulations of ACR-16/alpha7 AChRs, a consequent reduction in synaptic current, and predictable behavioral defects. Photoconversion experiments revealed defective translocation of ACR-16/alpha7 to synapses in Wnt-signaling mutants. Using optogenetic nerve stimulation, we demonstrate activity-dependent synaptic plasticity and its dependence on ACR-16/alpha7 translocation mediated by Wnt signaling via LIN-17/CAM-1 heteromeric receptors.
Rights and Permissions
Citation: Cell. 2012 Mar 30;149(1):173-87. Link to article on publisher's site
Jensen, Michael; Hoerndli, Frederic J.; Brockie, Penelope J.; Wang, Rui; Johnson, Erica; Maxfield, Dane; Francis, Michael M.; Madsen, David M.; and Maricq, Andres V., "Wnt signaling regulates acetylcholine receptor translocation and synaptic plasticity in the adult nervous system" (2012). Neurobiology Publications and Presentations. 102.