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PMID:22331845

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Citation

Chen, X and Ganetzky, B (2012) A neuropeptide signaling pathway regulates synaptic growth in Drosophila. J. Cell Biol. 196:529-43

Abstract

Neuropeptide signaling is integral to many aspects of neural communication, particularly modulation of membrane excitability and synaptic transmission. However, neuropeptides have not been clearly implicated in synaptic growth and development. Here, we demonstrate that cholecystokinin-like receptor (CCKLR) and drosulfakinin (DSK), its predicted ligand, are strong positive growth regulators of the Drosophila melanogaster larval neuromuscular junction (NMJ). Mutations of CCKLR or dsk produced severe NMJ undergrowth, whereas overexpression of CCKLR caused overgrowth. Presynaptic expression of CCKLR was necessary and sufficient for regulating NMJ growth. CCKLR and dsk mutants also reduced synaptic function in parallel with decreased NMJ size. Analysis of double mutants revealed that DSK/CCKLR regulation of NMJ growth occurs through the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding protein (CREB) pathway. Our results demonstrate a novel role for neuropeptide signaling in synaptic development. Moreover, because the cAMP-PKA-CREB pathway is required for structural synaptic plasticity in learning and memory, DSK/CCKLR signaling may also contribute to these mechanisms.

Links

PubMed PMC3283997 Online version:10.1083/jcb.201109044

Keywords

Animals; Animals, Genetically Modified; Cloning, Molecular; Cyclic AMP/metabolism; Cyclic AMP Response Element-Binding Protein/genetics; Cyclic AMP Response Element-Binding Protein/metabolism; Cyclic AMP-Dependent Protein Kinases/genetics; Cyclic AMP-Dependent Protein Kinases/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/genetics; Drosophila melanogaster/metabolism; Electrophysiology; Female; Immunoenzyme Techniques; Larva/growth & development; Larva/metabolism; Male; Mutation/genetics; Neuromuscular Junction/physiology; Neuropeptides/genetics; Neuropeptides/metabolism; Oligopeptides/genetics; Oligopeptides/metabolism; Presynaptic Terminals/metabolism; Receptors, Cholecystokinin/genetics; Receptors, Cholecystokinin/metabolism; Signal Transduction; Synapses/metabolism; Synaptic Transmission/physiology

Significance

Annotations

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

DROME:A8JUP8

colocalizes_with

GO:0043195: terminal bouton

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:A8JUP8

involved_in

GO:0007528: neuromuscular junction development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:A8JUP8

located_in

GO:0043025: neuronal cell body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:DSK

involved_in

GO:0007528: neuromuscular junction development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:CYA1

involved_in

GO:0007528: neuromuscular junction development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q1M2P7

colocalizes_with

GO:0043195: terminal bouton

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q1M2P7

involved_in

GO:0007528: neuromuscular junction development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q1M2P7

located_in

GO:0043025: neuronal cell body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:CREBB

involved_in

GO:0007528: neuromuscular junction development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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