140623 20240321220838.0 10.1523/JNEUROSCI.2038-18.2019 doi pmid:30696732 pmid pmc:PMC6445989 pmc 0270-6474 ISSN 1529-2401 ISSN altmetric:58447449 altmetric DZNE-2020-06945 English 610 Müller, Tanja M P:(DE-HGF)0 0 A Multiple Piccolino-RIBEYE Interaction Supports Plate-Shaped Synaptic Ribbons in Retinal Neurons. Washington, DC 2019 Soc.57413 online Crossref Society for Neuroscience 2019-01-29 print Crossref Society for Neuroscience 2019-04-03 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1677247124_7994 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote 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. 341 - Molecular Signaling (POF3-341) G:(DE-HGF)POF3-341 POF3-341 POF III 0 2019-10-03 Crossref https://creativecommons.org/licenses/by-nc-sa/4.0/ Dataset connected to CrossRef, PubMed, Alcohol Oxidoreductases: chemistry MeSH Alcohol Oxidoreductases: genetics MeSH Alcohol Oxidoreductases: metabolism MeSH Animals MeSH Co-Repressor Proteins: chemistry MeSH Co-Repressor Proteins: genetics MeSH Co-Repressor Proteins: metabolism MeSH Cytoskeletal Proteins: chemistry MeSH Cytoskeletal Proteins: genetics MeSH Cytoskeletal Proteins: metabolism MeSH HEK293 Cells MeSH Humans MeSH Mice MeSH Mice, Inbred C57BL MeSH Mice, Transgenic MeSH NIH 3T3 Cells MeSH Neuropeptides: chemistry MeSH Neuropeptides: genetics MeSH Neuropeptides: metabolism MeSH Protein Binding: physiology MeSH Protein Structure, Secondary MeSH Protein Structure, Tertiary MeSH Rats MeSH Rats, Sprague-Dawley MeSH Rats, Transgenic MeSH Retinal Neurons: metabolism MeSH Retinal Neurons: ultrastructure MeSH Synapses: genetics MeSH Synapses: metabolism MeSH Synapses: ultrastructure MeSH Gierke, Kaspar P:(DE-HGF)0 1 Joachimsthaler, Anneka P:(DE-HGF)0 2 Sticht, Heinrich P:(DE-HGF)0 3 Izsvák, Zsuzsanna P:(DE-HGF)0 4 Hamra, F Kent P:(DE-HGF)0 5 Fejtová, Anna P:(DE-HGF)0 6 Ackermann, Frauke P:(DE-2719)2810967 7 dzne Garner, Craig C P:(DE-2719)2810922 8 dzne Kremers, Jan P:(DE-HGF)0 9 Brandstätter, Johann H P:(DE-HGF)0 10 Regus-Leidig, Hanna P:(DE-HGF)0 11 Corresponding author 10.1523/jneurosci.2038-18.2019 Society for Neuroscience 2019-01-29 14 2606-2619 journal-article Crossref The Journal of Neuroscience 39 2019 0270-6474 10.1523/JNEUROSCI.2038-18.2019 Vol. 39, no. 14, p. 2606 - 2619 PERI:(DE-600)1475274-8 14 39:14<2606 - 2619 2606-2619 The journal of neuroscience 39 2019 0270-6474 Pubmed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445989 VDB oai:pub.dzne.de:140623 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 7 P:(DE-2719)2810967 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 8 P:(DE-2719)2810922 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-341 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Molecular Signaling 0 2019 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-13 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-13 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-13 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-13 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-13 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2022-11-13 JCR StatID:(DE-HGF)0100 StatID J NEUROSCI : 2021 2022-11-13 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2022-11-13 Peer Review StatID:(DE-HGF)0030 StatID ASC 2022-11-13 IF >= 5 StatID:(DE-HGF)9905 StatID J NEUROSCI : 2021 2022-11-13 I:(DE-2719)1810001 AG Garner Synaptopathy 0 I:(DE-2719)1813004 AG Ackermann Astrocyte - Synapse Interaction 1 journal VDB I:(DE-2719)1810001 I:(DE-2719)1813004 UNRESTRICTED 10.15252/embr.201540434 -- missing cx lookup -- Crossref 10.3389/fnsyn.2017.00014 -- missing cx lookup -- Crossref Cases-Langhoff 1996 Crossref Cases-Langhoff 1996 10.1523/JNEUROSCI.4240-11.2012 -- missing cx lookup -- Crossref 10.1002/cne.1344 -- missing cx lookup -- Crossref 10.1016/S0896-6273(03)00086-2 -- missing cx lookup -- Crossref 10.1016/S0896-6273(00)80883-1 -- missing cx lookup -- Crossref 10.1074/jbc.M210792200 -- missing cx lookup -- Crossref 10.1016/j.neuron.2010.10.027 -- missing cx lookup -- Crossref Crossref Frishman LJ (2006) Origins of the electroretinogram. In: Principles and practice of clinical electrophysiology of vision ( Heckenlively JR , Arden GB , eds), pp 139–183. London: MIT. 10.3389/fncel.2014.00060 -- missing cx lookup -- Crossref 10.1002/elps.1150181505 -- missing cx lookup -- Crossref 10.3389/fnsyn.2015.00019 -- missing cx lookup -- Crossref 10.1007/s10633-009-9194-5 -- missing cx lookup -- Crossref 10.15252/embj.201488796 -- missing cx lookup -- Crossref 10.1113/JP271826 -- missing cx lookup -- Crossref 10.1038/nature03418 -- missing cx lookup -- Crossref 10.1074/jbc.M212287200 -- missing cx lookup -- Crossref 10.1074/jbc.M000254200 -- missing cx lookup -- Crossref 10.1146/annurev-vision-082114-035709 -- missing cx lookup -- Crossref 10.1002/bies.1118 -- missing cx lookup -- Crossref 10.1523/JNEUROSCI.1964-08.2008 -- missing cx lookup -- Crossref 10.1038/nrn2924 -- missing cx lookup -- Crossref 10.1101/405985 -- missing cx lookup -- Crossref 10.1007/s00441-006-0276-3 -- missing cx lookup -- Crossref 10.1073/pnas.1002307107 -- missing cx lookup -- Crossref 10.1093/emboj/cdg283 -- missing cx lookup -- Crossref 10.1016/j.heares.2015.04.003 -- missing cx lookup -- Crossref 10.1113/JP274885 -- missing cx lookup -- Crossref 10.1002/jcc.20084 -- missing cx lookup -- Crossref 10.1111/j.1748-1716.2011.02355.x -- missing cx lookup -- Crossref 10.1371/journal.pone.0070373 -- missing cx lookup -- Crossref 10.3389/fncel.2014.00259 -- missing cx lookup -- Crossref 10.1146/annurev-neuro-061010-113705 -- missing cx lookup -- Crossref 10.1016/S0896-6273(00)00159-8 -- missing cx lookup -- Crossref 10.1016/S0896-6273(03)00207-1 -- missing cx lookup -- Crossref 10.1523/JNEUROSCI.2878-16.2017 -- missing cx lookup -- Crossref 10.1167/iovs.08-2758 -- missing cx lookup -- Crossref 10.1371/journal.pone.0167535 -- missing cx lookup -- Crossref 10.1083/jcb.200408157 -- missing cx lookup -- Crossref 10.1523/JNEUROSCI.0752-12.2012 -- missing cx lookup -- Crossref 10.1371/journal.pone.0120093 -- missing cx lookup -- Crossref 10.1523/JNEUROSCI.1835-11.2011 -- missing cx lookup -- Crossref 10.1038/emboj.2013.27 -- missing cx lookup -- Crossref 10.1083/jcb.147.1.151 -- missing cx lookup -- Crossref 10.1007/s00441-014-2102-7 -- missing cx lookup -- Crossref 10.1007/s12035-009-8058-z -- missing cx lookup -- Crossref 10.1152/physiol.00014.2004 -- missing cx lookup -- Crossref