Autocrine feedback maintains homeostatic neuropeptide expression in a peptidergic hub neuron

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ID: 332009
2026
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Abstract
Abstract Neuronal circuits sustain stable function by self-regulating their gene expression and neurosecretion. Patterns for autocrine feedback by neuropeptides are widespread across nervous systems, but how they contribute to neuronal homeostasis is less well understood. Here, we identify an autocrine homeostatic mechanism in a C. elegans peptidergic hub neuron. FLP-1 neuropeptide release activates the inhibitory receptor DMSR-7 on the AVK hub neurons to self-regulate flp-1 transcription, dense-core vesicle accumulation, and peptide secretion. We show that a parallel PDF-1/PDFR-1 pathway drives flp-1 expression, establishing a “push-and-pull” peptidergic feedback on the AVK neurons. AVK’s peptidergic output also depends on the number of FLP-1 peptides encoded in its precursor, revealing a dosage mechanism in behavioral regulation. Moreover, flp-1 expression coordinates transcript levels of additional neuropeptides in AVK. These findings uncover FLP-1 as a self-regulating homeostatic controller within a peptidergic hub neuron and fit a model where precursor-encoded redundancy supports stable yet adaptable circuit states.
Reference Key
openalex_W7221335187 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Luca Golinelli, Isabel Beets, Liesbet Temmerman
Journal current genetics
Year 2026
DOI
10.1093/genetics/iyag281
URL
https://doi.org/10.1093/genetics/iyag281
Keywords Keywords not found

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