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PMID:22464329

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Citation

Jensen, M, Hoerndli, FJ, Brockie, PJ, Wang, R, Johnson, E, Maxfield, D, Francis, MM, Madsen, DM and Maricq, AV (2012) Wnt signaling regulates acetylcholine receptor translocation and synaptic plasticity in the adult nervous system. Cell 149:173-87

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.

Links

PubMed PMC3375111 Online version:10.1016/j.cell.2011.12.038

Keywords

Animals; Caenorhabditis elegans/physiology; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Chromosome Pairing; Mutation; Nervous System; Neuromuscular Junction; Neuronal Plasticity; Receptor Protein-Tyrosine Kinases/genetics; Receptor Protein-Tyrosine Kinases/metabolism; Receptors, Cholinergic/metabolism; Receptors, G-Protein-Coupled/genetics; Receptors, G-Protein-Coupled/metabolism; Receptors, Nicotinic/genetics; Receptors, Nicotinic/metabolism; Wnt Proteins/metabolism; Wnt Signaling Pathway

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:G5EDV1

enables

GO:0030971: receptor tyrosine kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00000289

F

Seeded From UniProt

complete

CAEEL:CAM1

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00003006

F

Seeded From UniProt

complete

CAEEL:Q95Y45

enables

GO:0030971: receptor tyrosine kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00000289

F

Seeded From UniProt

complete


See also

References

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