Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Phosphorylation of presynaptic PLPPR3 controls synaptic vesicle release

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
7MB
[thumbnail of Supplemental Information]
Preview
PDF (Supplemental Information) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
793kB

Item Type:Article
Title:Phosphorylation of presynaptic PLPPR3 controls synaptic vesicle release
Creators Name:Kroon, Cristina, Bareesel, Shannon, Aguilar Perez, Gerard, Nagy-Herczeg, Domonkos, Ranti, Dimitra, Syropoulou, Vasiliki, Coveney, Sandra, Kirchner, Marieluise, Gimber, Niclas, Bintig, Willem, Brosig, Annika, Braune, Georg, Textoris-Taube, Kathrin, Zolnik, Timothy A., Mertins, Philipp, Schmoranzer, Jan, Milovanovic, Dragomir, Leondaritis, George and Eickholt, Britta J.
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.
Source:iScience
ISSN:2589-0042
Publisher:Elsevier / Cell Press
Volume:28
Number:9
Page Range:113435
Number of Pages:1
Date:19 September 2025
Official Publication:https://doi.org/10.1016/j.isci.2025.113435
Related to:

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library