TY  - JOUR
AU  - Müller, Tanja M
AU  - Gierke, Kaspar
AU  - Joachimsthaler, Anneka
AU  - Sticht, Heinrich
AU  - Izsvák, Zsuzsanna
AU  - Hamra, F Kent
AU  - Fejtová, Anna
AU  - Ackermann, Frauke
AU  - Garner, Craig C
AU  - Kremers, Jan
AU  - Brandstätter, Johann H
AU  - Regus-Leidig, Hanna
TI  - A Multiple Piccolino-RIBEYE Interaction Supports Plate-Shaped Synaptic Ribbons in Retinal Neurons.
JO  - The journal of neuroscience
VL  - 39
IS  - 14
SN  - 0270-6474
CY  - Washington, DC
PB  - Soc.57413
M1  - DZNE-2020-06945
SP  - 2606-2619
PY  - 2019
AB  - 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.
KW  - Alcohol Oxidoreductases: chemistry
KW  - Alcohol Oxidoreductases: genetics
KW  - Alcohol Oxidoreductases: metabolism
KW  - Animals
KW  - Co-Repressor Proteins: chemistry
KW  - Co-Repressor Proteins: genetics
KW  - Co-Repressor Proteins: metabolism
KW  - Cytoskeletal Proteins: chemistry
KW  - Cytoskeletal Proteins: genetics
KW  - Cytoskeletal Proteins: metabolism
KW  - HEK293 Cells
KW  - Humans
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Transgenic
KW  - NIH 3T3 Cells
KW  - Neuropeptides: chemistry
KW  - Neuropeptides: genetics
KW  - Neuropeptides: metabolism
KW  - Protein Binding: physiology
KW  - Protein Structure, Secondary
KW  - Protein Structure, Tertiary
KW  - Rats
KW  - Rats, Sprague-Dawley
KW  - Rats, Transgenic
KW  - Retinal Neurons: metabolism
KW  - Retinal Neurons: ultrastructure
KW  - Synapses: genetics
KW  - Synapses: metabolism
KW  - Synapses: ultrastructure
LB  - PUB:(DE-HGF)16
C6  - pmid:30696732
C2  - pmc:PMC6445989
DO  - DOI:10.1523/JNEUROSCI.2038-18.2019
UR  - https://pub.dzne.de/record/140623
ER  -