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The epithelial Na+ channel UNC-8 promotes an endocytic mechanism that recycles presynaptic components to new boutons in remodeling neurons.

Andrea Cuentas-Condori | Siqi Chen | Mia Krout | Kristin L Gallik | John Tipps | Casey Gailey | Leah Flautt | Hongkyun Kim | Ben Mulcahy | Mei Zhen | Janet E Richmond | David M Miller
Cell reports | 2023

Circuit refinement involves the formation of new presynaptic boutons as others are dismantled. Nascent presynaptic sites can incorporate material from recently eliminated synapses, but the recycling mechanisms remain elusive. In early-stage C. elegans larvae, the presynaptic boutons of GABAergic DD neurons are removed and new outputs established at alternative sites. Here, we show that developmentally regulated expression of the epithelial Na+ channel (ENaC) UNC-8 in remodeling DD neurons promotes a Ca2+ and actin-dependent mechanism, involving activity-dependent bulk endocytosis (ADBE), that recycles presynaptic material for reassembly at nascent DD synapses. ADBE normally functions in highly active neurons to accelerate local recycling of synaptic vesicles. In contrast, we find that an ADBE-like mechanism results in the distal recycling of synaptic material from old to new synapses. Thus, our findings suggest that a native mechanism (ADBE) can be repurposed to dismantle presynaptic terminals for reassembly at new, distant locations.

Pubmed ID: 37906594

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Associated grants

  • Agency: NICHD NIH HHS, United States
    Id: T32 HD007502
  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS106951
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS113559
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM125791
  • Agency: American Heart Association-American Stroke Association, United States
    Id: 18PRE33960581
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK020593

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Caenorhabditis Genetics Center (tool)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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