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bioRxiv · 10.1101/2022.11.29.518248

The Epithelial Na+ Channel UNC-8 promotes an endocytic mechanism that recycles presynaptic components from old to new boutons in remodeling neurons

Cuentas-Condori, A.·Chen, S.·Krout, M.·Gallick, K.·Tipps, J.·Flautt, L.·Richmond, J. E. E.·Miller, D. M.
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Abstract

SummaryPresynaptic terminals are actively relocated during development to refine circuit function, but the underlying cell biological mechanisms are largely unknown. In C. elegans, the presynaptic boutons of GABAergic DD neurons are moved to new locations during early larval development. We show that developmentally regulated expression of a presynaptic Epithelial Na+ Channel (ENaC), UNC-8, promotes a Ca2+-dependent mechanism, resembling Activity-Dependent Bulk Endocytosis (ADBE), that dismantles presynaptic material for reassembly at nascent DD synapses. ADBE normally functions in highly active neurons to accelerate local recycling of synaptic vesicles. We show that DD presynaptic remodeling depends on canonical features of ADBE including elevated intracellular Ca2+, the phosphatase Calcineurin and its targets, dynamin and the F-BAR protein syndapin, and Arp2/3-driven actin polymerization. Thus, our findings suggest that a native mechanism (ADBE) for maintaining neurotransmitter release at local synapses has been repurposed, in this case, to dismantle presynaptic terminals for reassembly at new locations. HighlightsO_LIDeveloping GABAergic neurons dismantle presynaptic terminals for reassembly at new locations. C_LIO_LIThe DEG/ENaC protein, UNC-8, promotes presynaptic disassembly and recycling C_LIO_LICa2+-dependent endocytosis drives presynaptic disassembly and recycling to new boutons C_LI

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Cuentas-Condori, A., Chen, S., Krout, M., Gallick, K., Tipps, J., Flautt, L., Richmond, J. E. E., Miller, D. M.. 2022-12-01. The Epithelial Na+ Channel UNC-8 promotes an endocytic mechanism that recycles presynaptic components from old to new boutons in remodeling neurons. https://doi.org/10.1101/2022.11.29.518248

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