TY  - JOUR
AU  - Kroon, Cristina
AU  - Bareesel, Shannon
AU  - Perez, Gerard Aguilar
AU  - Nagy-Herczeg, Domonkos
AU  - Ranti, Dimitra
AU  - Syropoulou, Vasiliki
AU  - Coveney, Sandra
AU  - Kirchner, Marieluise
AU  - Gimber, Niclas
AU  - Bintig, Willem
AU  - Brosig, Annika
AU  - Braune, Georg
AU  - Textoris-Taube, Kathrin
AU  - Zolnik, Timothy A.
AU  - Mertins, Philipp
AU  - Schmoranzer, Jan
AU  - Milovanovic, Dragomir
AU  - Leondaritis, George
AU  - Eickholt, Britta J.
TI  - Phosphorylation of presynaptic PLPPR3 controls synaptic vesicle release
JO  - iScience
VL  - 28
IS  - 9
SN  - 2589-0042
CY  - St. Louis
PB  - Elsevier
M1  - DZNE-2025-01117
SP  - 113435
PY  - 2025
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:41054519
DO  - DOI:10.1016/j.isci.2025.113435
UR  - https://pub.dzne.de/record/281370
ER  -