Wnt signaling regulates acetylcholine receptor translocation and synaptic plasticity in the adult nervous system
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Authors
Jensen, MichaelHoerndli, Frederic J.
Brockie, Penelope J.
Wang, Rui
Johnson, Erica
Maxfield, Dane
Francis, Michael M.
Madsen, David M.
Maricq, Andres V.
Document Type
Journal ArticlePublication Date
2012-03-30Keywords
AnimalsCaenorhabditis 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
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Show full item recordAbstract
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.Source
Cell. 2012 Mar 30;149(1):173-87. Link to article on publisher's siteDOI
10.1016/j.cell.2011.12.038Permanent Link to this Item
http://hdl.handle.net/20.500.14038/37835PubMed ID
22464329Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.cell.2011.12.038
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