A Multiple Piccolino-RIBEYE Interaction Supports Plate-Shaped Synaptic Ribbons in Retinal Neurons

Tanja M. Müller, Kaspar Gierke, Anneka Joachimsthaler, Heinrich Sticht, Zsuzsanna Izsvák, Franklin K Hamra, Anna Fejtová, Frauke Ackermann, Craig C. Garner, Jan Kremers, Johann H. Brandstätter, Hanna Regus-Leidig

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Active zones at chemical synapses are highly specialized sites for the regulated release of neurotransmitters. Despite a high degree of active zone protein conservation in vertebrates, every type of chemical synapse expresses a given set of protein isoforms and splice variants adapted to the demands on neurotransmitter release. So far, we know little about how specific active zone proteins contribute to the structural and functional diversity of active zones. In this study, we explored the nanodomain organization of ribbon-type active zones by addressing the significance of Piccolino, the ribbon synapse-specific splice variant of Piccolo, for shaping the ribbon structure. We followed up on previous results, which indicated that rod photoreceptor synaptic ribbons lose their structural integrity in a knockdown of Piccolino. Here, we demonstrate an interaction between Piccolino and the major ribbon component RIBEYE that supports plate-shaped synaptic ribbons in retinal neurons. In a detailed ultrastructural analysis of three different types of retinal ribbon synapses in Piccolo/Piccolino-deficient male and female rats, we show that the absence of Piccolino destabilizes the superstructure of plate-shaped synaptic ribbons, although with variable manifestation in the cell types examined. Our analysis illustrates how the expression of a specific active zone protein splice variant (e.g., Piccolino) contributes to structural diversity of vertebrate active zones.SIGNIFICANCE STATEMENT Retinal ribbon synapses are a specialized type of chemical synapse adapted for the regulated fast and tonic release of neurotransmitter. The hallmark of retinal ribbon synapses is the plate-shaped synaptic ribbon, which extends from the release site into the terminals' cytoplasm and tethers hundreds of synaptic vesicles. Here, we show that Piccolino, the synaptic ribbon specific splice variant of Piccolo, interacts with RIBEYE, the main component of synaptic ribbons. This interaction occurs via several PxDLS-like motifs located at the C terminus of Piccolino, which can connect multiple RIBEYE molecules. Loss of Piccolino disrupts the characteristic plate-shaped structure of synaptic ribbons, indicating a role of Piccolino in synaptic ribbon assembly.

Original languageEnglish (US)
Pages (from-to)2606-2619
Number of pages14
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume39
Issue number14
DOIs
StatePublished - Apr 3 2019

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Retinal Neurons
Synapses
Neurotransmitter Agents
Protein Isoforms
Vertebrates
Retinal Rod Photoreceptor Cells
Synaptic Vesicles
Cytoplasm
Proteins

Keywords

  • active zone
  • photoreceptor
  • Piccolino
  • ribbon synapse
  • RIBEYE

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A Multiple Piccolino-RIBEYE Interaction Supports Plate-Shaped Synaptic Ribbons in Retinal Neurons. / Müller, Tanja M.; Gierke, Kaspar; Joachimsthaler, Anneka; Sticht, Heinrich; Izsvák, Zsuzsanna; Hamra, Franklin K; Fejtová, Anna; Ackermann, Frauke; Garner, Craig C.; Kremers, Jan; Brandstätter, Johann H.; Regus-Leidig, Hanna.

In: The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 39, No. 14, 03.04.2019, p. 2606-2619.

Research output: Contribution to journalArticle

Müller, TM, Gierke, K, Joachimsthaler, A, Sticht, H, Izsvák, Z, Hamra, FK, Fejtová, A, Ackermann, F, Garner, CC, Kremers, J, Brandstätter, JH & Regus-Leidig, H 2019, 'A Multiple Piccolino-RIBEYE Interaction Supports Plate-Shaped Synaptic Ribbons in Retinal Neurons', The Journal of neuroscience : the official journal of the Society for Neuroscience, vol. 39, no. 14, pp. 2606-2619. https://doi.org/10.1523/JNEUROSCI.2038-18.2019
Müller, Tanja M. ; Gierke, Kaspar ; Joachimsthaler, Anneka ; Sticht, Heinrich ; Izsvák, Zsuzsanna ; Hamra, Franklin K ; Fejtová, Anna ; Ackermann, Frauke ; Garner, Craig C. ; Kremers, Jan ; Brandstätter, Johann H. ; Regus-Leidig, Hanna. / A Multiple Piccolino-RIBEYE Interaction Supports Plate-Shaped Synaptic Ribbons in Retinal Neurons. In: The Journal of neuroscience : the official journal of the Society for Neuroscience. 2019 ; Vol. 39, No. 14. pp. 2606-2619.
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