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PMID:18280750

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Citation

Pan, L, Woodruff, E 3rd, Liang, P and Broadie, K (2008) Mechanistic relationships between Drosophila fragile X mental retardation protein and metabotropic glutamate receptor A signaling. Mol. Cell. Neurosci. 37:747-60

Abstract

Fragile X syndrome is caused by loss of the FMRP translational regulator. A current hypothesis proposes that FMRP functions downstream of mGluR signaling to regulate synaptic connections. Using the Drosophila disease model, we test relationships between dFMRP and the sole Drosophila mGluR (DmGluRA) by assaying protein expression, behavior and neuron structure in brain and NMJ; in single mutants, double mutants and with an mGluR antagonist. At the protein level, dFMRP is upregulated in dmGluRA mutants, and DmGluRA is upregulated in dfmr1 mutants, demonstrating mutual negative feedback. Null dmGluRA mutants display defects in coordinated movement behavior, which are rescued by removing dFMRP expression. Null dfmr1 mutants display increased NMJ presynaptic structural complexity and elevated presynaptic vesicle pools, which are rescued by blocking mGluR signaling. Null dfmr1 brain neurons similarly display increased presynaptic architectural complexity, which is rescued by blocking mGluR signaling. These data show that DmGluRA and dFMRP convergently regulate presynaptic properties.

Links

PubMed PMC3989938 Online version:10.1016/j.mcn.2008.01.003

Keywords

Animals; Behavior, Animal/physiology; Drosophila; Drosophila Proteins/genetics; Drosophila Proteins/physiology; Fragile X Mental Retardation Protein/genetics; Fragile X Mental Retardation Protein/physiology; Movement/physiology; Mutation; Neuromuscular Junction/physiology; Neuromuscular Junction/ultrastructure; Receptors, Metabotropic Glutamate/genetics; Receptors, Metabotropic Glutamate/physiology; Signal Transduction/genetics; Signal Transduction/physiology

Significance

Annotations

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

DROME:GRM

involved_in

GO:0072553: terminal button organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:FMR1

involved_in

GO:0070142: synaptic vesicle budding

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:FMR1

involved_in

GO:0097091: synaptic vesicle clustering

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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