281370 20260105130618.0 pmc:PMC12496174 pmc 10.1016/j.isci.2025.113435 doi altmetric:180730753 altmetric pmid:41054519 pmid DZNE-2025-01117 050 Kroon, Cristina 0 Phosphorylation of presynaptic PLPPR3 controls synaptic vesicle release St. Louis 2025 Elsevier article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1759836611_17317 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Phospholipid-phosphatase-related protein 3 (PLPPR3) belongs to a family of transmembrane proteins highly expressed in the nervous system where it regulates critical axonal growth processes during guidance, filopodia formation, and branching. However, little is known regarding its role in synapses and the signaling events regulating PLPPR3 function. Here, we identify 26 high-confidence phosphorylation sites in the intracellular domain of PLPPR3 using mass spectrometry. Biochemical characterization established one of these-S351-as a bona fide phosphorylation site of protein kinase A (PKA). PLPPR3 is enriched at presynaptic terminals, and deletion of PLPPR3 results in increased depolarization-induced synaptic vesicle release in hippocampal neurons. This tonic inhibitory signal toward depolarization-induced presynaptic activity is corrected by expression of PLPPR3 intracellular domain, but not a S351A phospho-dead mutant, in Plppr3 -/- hippocampal neurons. We propose that PLPPR3 phosphorylation under the control of PKA activity is a signaling integrator of presynaptic activity in hippocampal neurons. 351 - Brain Function (POF4-351) G:(DE-HGF)POF4-351 POF4-351 POF IV 0 Dataset connected to CrossRef, Journals: pub.dzne.de Bareesel, Shannon 1 Perez, Gerard Aguilar P:(DE-2719)9002012 2 dzne Nagy-Herczeg, Domonkos 3 Ranti, Dimitra 4 Syropoulou, Vasiliki 5 Coveney, Sandra 6 Kirchner, Marieluise 7 Gimber, Niclas 8 Bintig, Willem 9 Brosig, Annika 10 Braune, Georg 11 Textoris-Taube, Kathrin 12 Zolnik, Timothy A. 13 Mertins, Philipp 14 Schmoranzer, Jan 15 Milovanovic, Dragomir P:(DE-2719)9000670 16 dzne Leondaritis, George 17 Eickholt, Britta J. 0000-0001-7873-8687 18 10.1016/j.isci.2025.113435 Vol. 28, no. 9, p. 113435 - PERI:(DE-600)2927064-9 9 113435 iScience 28 2025 2589-0042 http://pub.dzne.de/record/281370/files/DZNE-2025-01117%20SUP.pdf OpenAccess http://pub.dzne.de/record/281370/files/DZNE-2025-01117.pdf pdfa http://pub.dzne.de/record/281370/files/DZNE-2025-01117%20SUP.pdf?subformat=pdfa OpenAccess pdfa http://pub.dzne.de/record/281370/files/DZNE-2025-01117.pdf?subformat=pdfa oai:pub.dzne.de:281370 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)9002012 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 16 P:(DE-2719)9000670 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-351 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Brain Function 0 2025 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2025-01-02 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2025-01-02 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2025-01-02 Creative Commons Attribution CC BY 4.0 LIC:(DE-HGF)CCBY4 HGFVOC JCR StatID:(DE-HGF)0100 StatID ISCIENCE : 2022 2025-01-02 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2023-04-12T14:51:15Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2023-04-12T14:51:15Z WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2025-01-02 Fees StatID:(DE-HGF)0700 StatID 2025-01-02 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2025-01-02 OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Anonymous peer review 2023-04-12T14:51:15Z Article Processing Charges StatID:(DE-HGF)0561 StatID 2025-01-02 IF >= 5 StatID:(DE-HGF)9905 StatID ISCIENCE : 2022 2025-01-02 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2025-01-02 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2025-01-02 I:(DE-2719)1813002 AG Milovanovic (Berlin) Molecular Neuroscience 0 journal VDB UNRESTRICTED I:(DE-2719)1813002 FullTexts