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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},
pubmed = {pmid:41054519},
doi = {10.1016/j.isci.2025.113435},
url = {https://pub.dzne.de/record/281370},
}