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@ARTICLE{Kroon:281370,
author = {Kroon, Cristina and Bareesel, Shannon and Perez, Gerard
Aguilar and Nagy-Herczeg, Domonkos and Ranti, Dimitra and
Syropoulou, Vasiliki and Coveney, Sandra and Kirchner,
Marieluise and Gimber, Niclas and Bintig, Willem and Brosig,
Annika and Braune, Georg and Textoris-Taube, Kathrin and
Zolnik, Timothy A. and Mertins, Philipp and Schmoranzer, Jan
and Milovanovic, Dragomir and Leondaritis, George and
Eickholt, Britta J.},
title = {{P}hosphorylation of presynaptic {PLPPR}3 controls synaptic
vesicle release},
journal = {iScience},
volume = {28},
number = {9},
issn = {2589-0042},
address = {St. Louis},
publisher = {Elsevier},
reportid = {DZNE-2025-01117},
pages = {113435},
year = {2025},
abstract = {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.},
cin = {AG Milovanovic (Berlin)},
ddc = {050},
cid = {I:(DE-2719)1813002},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC12496174},
pubmed = {pmid:41054519},
doi = {10.1016/j.isci.2025.113435},
url = {https://pub.dzne.de/record/281370},
}