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@ARTICLE{Mller:140623,
author = {Müller, Tanja M and Gierke, Kaspar and Joachimsthaler,
Anneka and Sticht, Heinrich and Izsvák, Zsuzsanna and
Hamra, F Kent and Fejtová, Anna and Ackermann, Frauke and
Garner, Craig C and Kremers, Jan and Brandstätter, Johann H
and Regus-Leidig, Hanna},
title = {{A} {M}ultiple {P}iccolino-{RIBEYE} {I}nteraction
{S}upports {P}late-{S}haped {S}ynaptic {R}ibbons in
{R}etinal {N}eurons.},
journal = {The journal of neuroscience},
volume = {39},
number = {14},
issn = {0270-6474},
address = {Washington, DC},
publisher = {Soc.57413},
reportid = {DZNE-2020-06945},
pages = {2606-2619},
year = {2019},
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.},
keywords = {Alcohol Oxidoreductases: chemistry / Alcohol
Oxidoreductases: genetics / Alcohol Oxidoreductases:
metabolism / Animals / Co-Repressor Proteins: chemistry /
Co-Repressor Proteins: genetics / Co-Repressor Proteins:
metabolism / Cytoskeletal Proteins: chemistry / Cytoskeletal
Proteins: genetics / Cytoskeletal Proteins: metabolism /
HEK293 Cells / Humans / Mice / Mice, Inbred C57BL / Mice,
Transgenic / NIH 3T3 Cells / Neuropeptides: chemistry /
Neuropeptides: genetics / Neuropeptides: metabolism /
Protein Binding: physiology / Protein Structure, Secondary /
Protein Structure, Tertiary / Rats / Rats, Sprague-Dawley /
Rats, Transgenic / Retinal Neurons: metabolism / Retinal
Neurons: ultrastructure / Synapses: genetics / Synapses:
metabolism / Synapses: ultrastructure},
cin = {AG Garner / AG Ackermann},
ddc = {610},
cid = {I:(DE-2719)1810001 / I:(DE-2719)1813004},
pnm = {341 - Molecular Signaling (POF3-341)},
pid = {G:(DE-HGF)POF3-341},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30696732},
pmc = {pmc:PMC6445989},
doi = {10.1523/JNEUROSCI.2038-18.2019},
url = {https://pub.dzne.de/record/140623},
}