The missing link: Piccolino is essential for tethering synaptic vesicles to rod photoreceptor ribbons.
Overview
- Department of Biology, Animal Physiology/Neurobiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Center for Biostructural Imaging of Neurodegeneration (BIN), University Medical Center Göttingen, Göttingen, Germany
- Molecular Architecture of Synapses Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany
- Göttingen Graduate School for Neuroscience, Biophysics and Molecular Biosciences, University of Göttingen, Göttingen, Germany
- Department of Biology, Computational Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Erlangen National High-Performance Computing Center, Erlangen, Germany
- FAU Profile Center Immunomedicine (FAU I-MED), Erlangen, Germany
Abstract
Retinal photoreceptors transmit light signals to their postsynaptic neurons with high precision, speed and without fatigue. This high-throughput neurotransmission relies on a sophisticated molecular machinery centered on a presynaptic organelle, the synaptic ribbon (SR). A hallmark of SRs is the recruitment of synaptic vesicles (SVs) from the cytoplasmic SV pool via “tethering”. However, the identity of the tether and the mechanism underlying SV tethering are unknown. Here, we show that cell-specific deletion of the SR-associated protein Piccolino from rod photoreceptors disrupts SR morphology and ablates SV tethering. Nanoscale epitope mapping suggests that Piccolino acts as an SV tether by extending its N terminus away from the SR into the SV-filled terminal cytoplasm. With in silico modeling and protein lipid-binding assays, we demonstrate that an amphipathic liquid packing sensor motif (ALPS) at the N terminus of Piccolino binds SV-like liposomes, implicating this interaction as the mechanism underlying SV tethering. Together, our findings identified Piccolino as the molecular link between the SR and SVs.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- zenodo:20762753, at Zenodo; found in “Data availability”
Data availability
The uncropped Blots displayed in Figs. 1, 5 and S3 are available in the data. The numerical data underlying each figure are openly available in Zenodo (accession number: https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 2, 28 September 2026
- Publisher: n/a → Rockefeller University Press
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 16 authors, 9 MeSH terms, 5 funders, 87 references.
Cite
This paper
Gierke, K., Gadomska, M., Breuer, J., Bahr, J. N., Müller, T. M., Ehnis, H., Zobel, S., Mejia Villagran, N., Kirsch, S. A., Skrzypek, A., Frischknecht, R., Fejtová, A., Böckmann, R. A., Wichmann, C., Regus-Leidig, H., & Brandstätter, J. H. (2026). The missing link: Piccolino is essential for tethering synaptic vesicles to rod photoreceptor ribbons. The Journal of cell biology, 225(9), e202509110. https://
BibTeX
@article{gierke2026missi
author = {Gierke, Kaspar and Gadomska, Michalina and Breuer, Julia and Bahr, Julius N. and Müller, Tanja M. and Ehnis, Hanna and Zobel, Sina and Mejia Villagran, Nancy and Kirsch, Sonja A. and Skrzypek, Alexandra and Frischknecht, Renato and Fejtová, Anna and Böckmann, Rainer A. and Wichmann, Carolin and Regus-Leidig, Hanna and Brandstätter, Johann Helmut},
title = {{The missing link: Piccolino is essential for tethering synaptic vesicles to rod photoreceptor ribbons}},
journal = {The Journal of cell biology},
year = {2026},
month = jul,
volume = {225},
number = {9},
pages = {e202509110},
publisher = {Rockefeller University Press},
issn = {0021-9525},
doi = {10.1083/
url = {https://
pmid = {42489669},
pmcid = {PMC13394108}
}
RIS
TY - JOUR
AU - Gierke, Kaspar
AU - Gadomska, Michalina
AU - Breuer, Julia
AU - Bahr, Julius N.
AU - Müller, Tanja M.
AU - Ehnis, Hanna
AU - Zobel, Sina
AU - Mejia Villagran, Nancy
AU - Kirsch, Sonja A.
AU - Skrzypek, Alexandra
AU - Frischknecht, Renato
AU - Fejtová, Anna
AU - Böckmann, Rainer A.
AU - Wichmann, Carolin
AU - Regus-Leidig, Hanna
AU - Brandstätter, Johann Helmut
TI - The missing link: Piccolino is essential for tethering synaptic vesicles to rod photoreceptor ribbons
T2 - The Journal of cell biology
J2 - J Cell Biol
PY - 2026
DA - 2026/
VL - 225
IS - 9
SP - e202509110
SN - 0021-9525
PB - Rockefeller University Press
DO - 10.1083/
UR - https://
LA - en
ER -
CSL-JSON
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