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000281370 1001_ $$aKroon, Cristina$$b0
000281370 245__ $$aPhosphorylation of presynaptic PLPPR3 controls synaptic vesicle release
000281370 260__ $$aSt. Louis$$bElsevier$$c2025
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000281370 520__ $$aPhospholipid-phosphatase-related protein 3 (PLPPR3) belongs to a family of transmembrane proteins highly expressed in the nervous system where it regulates critical axonal growth processes during guidance, filopodia formation, and branching. However, little is known regarding its role in synapses and the signaling events regulating PLPPR3 function. Here, we identify 26 high-confidence phosphorylation sites in the intracellular domain of PLPPR3 using mass spectrometry. Biochemical characterization established one of these—S351—as a bona fide phosphorylation site of protein kinase A (PKA). PLPPR3 is enriched at presynaptic terminals, and deletion of PLPPR3 results in increased depolarization-induced synaptic vesicle release in hippocampal neurons. This tonic inhibitory signal toward depolarization-induced presynaptic activity is corrected by expression of PLPPR3 intracellular domain, but not a S351A phospho-dead mutant, in Plppr3−/− hippocampal neurons. We propose that PLPPR3 phosphorylation under the control of PKA activity is a signaling integrator of presynaptic activity in hippocampal neurons.
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000281370 7001_ $$aBareesel, Shannon$$b1
000281370 7001_ $$0P:(DE-2719)9002012$$aPerez, Gerard Aguilar$$b2$$udzne
000281370 7001_ $$aNagy-Herczeg, Domonkos$$b3
000281370 7001_ $$aRanti, Dimitra$$b4
000281370 7001_ $$aSyropoulou, Vasiliki$$b5
000281370 7001_ $$aCoveney, Sandra$$b6
000281370 7001_ $$aKirchner, Marieluise$$b7
000281370 7001_ $$aGimber, Niclas$$b8
000281370 7001_ $$aBintig, Willem$$b9
000281370 7001_ $$aBrosig, Annika$$b10
000281370 7001_ $$aBraune, Georg$$b11
000281370 7001_ $$aTextoris-Taube, Kathrin$$b12
000281370 7001_ $$aZolnik, Timothy A.$$b13
000281370 7001_ $$aMertins, Philipp$$b14
000281370 7001_ $$aSchmoranzer, Jan$$b15
000281370 7001_ $$0P:(DE-2719)9000670$$aMilovanovic, Dragomir$$b16$$udzne
000281370 7001_ $$aLeondaritis, George$$b17
000281370 7001_ $$00000-0001-7873-8687$$aEickholt, Britta J.$$b18
000281370 773__ $$0PERI:(DE-600)2927064-9$$a10.1016/j.isci.2025.113435$$gVol. 28, no. 9, p. 113435 -$$n9$$p113435$$tiScience$$v28$$x2589-0042$$y2025
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