title: Wnt signaling regulates acetylcholine receptor translocation and synaptic plasticity in the adult nervous system.
abstract: 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/α7 AChRs, a consequent reduction in synaptic current, and predictable behavioral defects. Photoconversion experiments revealed defective translocation of ACR-16/α7 to synapses in Wnt-signaling mutants. Using optogenetic nerve stimulation, we demonstrate activity-dependent synaptic plasticity and its dependence on ACR-16/α7 translocation mediated by Wnt signaling via LIN-17/CAM-1 heteromeric receptors.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112-0840, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Jensen
authors.forename: Frédéric J
authors.initials: FJ
authors.lastname: Hoerndli
authors.forename: Penelope J
authors.initials: PJ
authors.lastname: Brockie
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Erica
authors.initials: E
authors.lastname: Johnson
authors.forename: Dane
authors.initials: D
authors.lastname: Maxfield
authors.forename: Michael M
authors.initials: MM
authors.lastname: Francis
authors.forename: David M
authors.initials: DM
authors.lastname: Madsen
authors.forename: Andres V
authors.initials: AV
authors.lastname: Maricq
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D023902:Chromosome Pairing; D009154:Mutation; D009420:Nervous System; D009469:Neuromuscular Junction; D009473:Neuronal Plasticity; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D011950:Receptors, Cholinergic / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: C544875:CWN-2 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C101684:LIN-17 protein, C elegans; D011950:Receptors, Cholinergic; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D051153:Wnt Proteins; C099378:acr-16 protein, C elegans; C526267:CAM-1 protein, C elegans; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors