FMRP sustains presynaptic function via control of activity-dependent bulk endocytosis
FMRP sustains presynaptic function via control of activity-dependent bulk endocytosis
SUMMARY Synaptic vesicle (SV) recycling defects are linked to a number of neurodevelopmental disorders, including fragile X syndrome (FXS), which results from loss of fragile X mental retardation protein (FMRP) encoded by the FMR1 gene. Since defects in SV recycling are exacerbated during intense neuronal activity, we investigated whether these events were disproportionately affected by the absence of FMRP. We revealed that primary neuronal cultures from a Fmr1 knockout rat model display a specific defect in activity-dependent bulk endocytosis (ADBE). This defect resulted in an inability of Fmr1 knockout neurons to sustain SV recycling during high frequency stimulation. Using a molecular replacement strategy, we also revealed that a human FMRP interaction mutant failed to correct ADBE dysfunction in knockout neurons, however this dysfunction could be corrected by BK channel agonists. Therefore, FMRP performs a key role in sustaining neurotransmitter release via selective control of the endocytosis mode, ADBE.
Bonnycastle Katherine、Kind Peter C.、Cousin Michael A.
Centre for Discovery Brain Sciences, Hugh Robson Building, George Square, University of Edinburgh||Patrick Wild Centre, Hugh Robson Building, George Square, University of Edinburgh||Simons Initiative for the Developing Brain, Hugh Robson Building, George Square, University of EdinburghCentre for Discovery Brain Sciences, Hugh Robson Building, George Square, University of Edinburgh||Patrick Wild Centre, Hugh Robson Building, George Square, University of Edinburgh||Simons Initiative for the Developing Brain, Hugh Robson Building, George Square, University of EdinburghCentre for Discovery Brain Sciences, Hugh Robson Building, George Square, University of Edinburgh||Patrick Wild Centre, Hugh Robson Building, George Square, University of Edinburgh||Simons Initiative for the Developing Brain, Hugh Robson Building, George Square, University of Edinburgh
神经病学、精神病学基础医学分子生物学
FMRPneuronendocytosisvesicleneurotransmitterfragile X syndrome
Bonnycastle Katherine,Kind Peter C.,Cousin Michael A..FMRP sustains presynaptic function via control of activity-dependent bulk endocytosis[EB/OL].(2025-03-28)[2025-05-01].https://www.biorxiv.org/content/10.1101/2020.09.10.291062.点此复制
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