The missing link: Piccolino is essential for tethering synaptic vesicles to rod photoreceptor ribbons

Gierke K, Gadomska M, Breuer J, Bahr JN, Müller T, Ehnis H, Zobel S, Mejia Villagran N, Kirsch S, Skrzypek A, Frischknecht R, Fejtová A, Böckmann R, Wichmann C, Regus-Leidig H, Brandstätter JH (2026)

Publication Type: Journal article

Publication year: 2026

Journal

The Journal of Cell Biology Rockefeller University Press

Book Volume: 225

Journal Issue: 9

DOI: 10.1083/jcb.202509110

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.

Authors with CRIS profile

Kaspar Gierke Lehrstuhl für Tierphysiologie Michalina Gadomska Lehrstuhl für Tierphysiologie Julia Breuer Department Biologie Tanja Müller Lehrstuhl für Tierphysiologie Hanna Ehnis Interdisziplinäres Zentrum für Klinische Forschung IZKF-Förderlinien Nancy Mejia Villagran Professur für Computational Biology Sonja Kirsch Professur für Computational Biology Renato Frischknecht Lehrstuhl für Tierphysiologie Anna Fejtová Department of Psychiatry and Psychotherapy Rainer Böckmann Professur für Computational Biology Hanna Regus-Leidig Lehrstuhl für Tierphysiologie Johann Helmut Brandstätter Lehrstuhl für Tierphysiologie

Involved external institutions

Universitätsklinikum Göttingen DE Germany (DE)

How to cite

APA:

Gierke, K., Gadomska, M., Breuer, J., Bahr, J.N., Müller, T., Ehnis, 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). https://doi.org/10.1083/jcb.202509110

MLA:

Gierke, Kaspar, et al. "The missing link: Piccolino is essential for tethering synaptic vesicles to rod photoreceptor ribbons." The Journal of Cell Biology 225.9 (2026).

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