Cell-intrinsic regulation of presynaptic release site patterning
- 1Albert Einstein College of Medicine
Abstract
Functional neuronal connectivity depends not only on synaptic partner choice but also on the number, strength, and spatial distribution of release sites between partners. How these features are regulated remains poorly understood. Here, using the C. elegans DA9 motor neuron, we identify the immunoglobulin superfamily cell adhesion molecules SYG-1 and SYG-2 as cell-autonomous regulators of presynaptic release-site patterning. SYG-2 regulates presynapse number, size, and spacing, whereas SYG-1 primarily regulates spacing. Endogenous localization and cell-specific knockout analyses reveal that SYG-2 recruits SYG-1 to the presynaptic domain through previously unrecognized cis interactions. Endogenous structure-function studies further demonstrate that the SYG-2 intracellular domain is required for presynaptic organization and can promote presynapse formation independently of its extracellular domain. Genetic and targeted actin-disruption experiments implicate the adaptor protein NCK-1 and local actin remodeling in SYG-2 intracellular signaling. Together, these findings reveal how cell adhesion molecules can act cell-intrinsically to pattern presynaptic release sites after synaptic partners have been established.
Related
- Presynaptic filopodia form kinapses and promote convective membrane flow to sustain synchronous neurotransmitter release
- α2δ-2 mediates coupling of presynaptic calcium entry to vesicle release in hippocampal parvalbumin-expressing interneurons
- Cell-type specific and nanoscale control of hippocampal presynaptic homeostatic plasticity
- SOMATODENDRITIC VASOPRESSIN RELEASE COUPLES INTRINSIC EXCITABILITY TO POPULATION-LEVEL ACTIVITY
- Temporal regulation of a spatial patterning factor in Drosophila neurogenesis
BibTeX
@misc{summerville2026cellintrinsic,
title = {{Cell-intrinsic regulation of presynaptic release site patterning}},
author = {J. D. Summerville and E. B. Frankel and Y. Dong and J. Bai and P. T. Kurshan},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.02.756300},
url = {https://www.biorxiv.org/content/10.64898/2026.10.02.756300v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Cell-intrinsic regulation of presynaptic release site patterning
AU - J. D. Summerville
AU - E. B. Frankel
AU - Y. Dong
AU - J. Bai
AU - P. T. Kurshan
PY - 2026
DA - 2026/10/02
PB - bioRxiv
DO - 10.64898/2026.10.02.756300
UR - https://www.biorxiv.org/content/10.64898/2026.10.02.756300v1
AB - Functional neuronal connectivity depends not only on synaptic partner choice but also on the number, strength, and spatial distribution of release sites between partners. How these features are regulated remains poorly understood. Here, using the C. elegans DA9 motor neuron, we identify the immunoglobulin superfamily cell adhesion molecules SYG-1 and SYG-2 as cell-autonomous regulators of presynaptic release-site patterning. SYG-2 regulates presynapse number, size, and spacing, whereas SYG-1 primarily regulates spacing. Endogenous localization and cell-specific knockout analyses reveal that SYG-2 recruits SYG-1 to the presynaptic domain through previously unrecognized cis interactions. Endogenous structure-function studies further demonstrate that the SYG-2 intracellular domain is required for presynaptic organization and can promote presynapse formation independently of its extracellular domain. Genetic and targeted actin-disruption experiments implicate the adaptor protein NCK-1 and local actin remodeling in SYG-2 intracellular signaling. Together, these findings reveal how cell adhesion molecules can act cell-intrinsically to pattern presynaptic release sites after synaptic partners have been established.
ER -