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• W1925610384 abstract "Transforming growth factor-β (TGF-β) family signaling pathways have roles in both neuronal development and the regulation of synaptic function. Here we identify a novel role for the Caenorhabditis elegans DAF-7/TGF-β signaling pathway in the regulation of the AMPA-type glutamate receptor GLR-1. We found that the abundance of GLR-1 increases at synapses in the ventral nerve cord (VNC) of animals with loss-of-function mutations in multiple DAF-7/TGF-β pathway components including the TGF-β ligand DAF-7, the type I receptor DAF-1, and the Smads DAF-8 and DAF-14. The GLR-1 defect can be rescued by expression of daf-8 specifically in glr-1-expressing interneurons. The effect on GLR-1 was specific for the DAF-7 pathway because mutations in the DBL-1/TGF-β family pathway did not increase GLR-1 levels in the VNC. Immunoblot analysis indicates that total levels of GLR-1 protein are increased in neurons of DAF-7/TGF-β pathway mutants. The increased abundance of GLR-1 in the VNC of daf-7 pathway mutants is dependent on the transcriptional regulator DAF-3/Smad suggesting that DAF-3-dependent transcription controls GLR-1 levels. Furthermore, we found that glr-1 transcription is increased in daf-7 mutants based on a glr-1 transcriptional reporter. Together these results suggest that the DAF-7/TGF-β signaling pathway functions in neurons and negatively regulates the abundance of GLR-1, in part, by controlling transcription of the receptor itself. Finally, DAF-7/TGF-β pathway mutants exhibit changes in spontaneous locomotion that are dependent on endogenous GLR-1 and consistent with increased glutamatergic signaling. These results reveal a novel mechanism by which TGF-β signaling functions in the nervous system to regulate behavior." @default.
• W1925610384 created "2016-06-24" @default.
• W1925610384 creator A5004506135 @default.
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• W1925610384 date "2015-07-01" @default.
• W1925610384 modified "2023-10-10" @default.
• W1925610384 title "The DAF-7/TGF-β signaling pathway regulates abundance of the Caenorhabditis elegans glutamate receptor GLR-1" @default.
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• W1925610384 doi "https://doi.org/10.1016/j.mcn.2015.06.003" @default.
• W1925610384 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4540650" @default.
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