{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:08:09Z","timestamp":1788876489730,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T00:00:00Z","timestamp":1720742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 958, TP A16"],"award-info":[{"award-number":["SFB 958, TP A16"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR186, TP A10"],"award-info":[{"award-number":["TRR186, TP A10"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lysophosphatidic acid (LPA) is a bioactive phospholipid that participates in critical processes in neural development and adult brain function and is implicated in various pathophysiological conditions. Along with its six well\u2010characterized receptors, atypical regulators of LPA signaling have also been suggested, including phospholipid phosphatase\u2010related proteins (PLPPRs). PLPPRs have been mostly studied in the developing brain where they control LPA\u2010dependent axon guidance, cortical network hyperexcitability, and glutamatergic neurotransmission. PLPPR4 and PLPPR3 represent two closely related proteins reported to localize predominantly in dendrites and axons, respectively, and differ in their developmental expression patterns. Herein, we have revised the expression patterns of PLPPRs in the cerebellum, dorsal and ventral hippocampus, prefrontal cortex (PFC), nucleus accumbens, and striatum during development and in the adult using quantitative PCR. Expression patterns of <jats:italic>Plppr2,4<\/jats:italic> and <jats:italic>5<\/jats:italic> were consistent with previous studies, whereas <jats:italic>Plppr3<\/jats:italic> and <jats:italic>Plppr1<\/jats:italic> exhibited a unique expression profile in nucleus accumbens (NAc) and striatum in later developmental and adult stages, which we verified at the protein level for PLPPR3. To investigate neuron type\u2010specific expression at the single cell level, we developed a bioinformatic tool to analyze recent single\u2010cell RNA\u2010sequencing data in the cerebral cortex and hippocampus of adult mice. Our analysis revealed a widespread but also selective adult neuron\u2010type expression with higher expression levels of <jats:italic>Plppr3, Plppr1, and Plppr5<\/jats:italic> in GABAergic and <jats:italic>Plppr4<\/jats:italic> and <jats:italic>Plppr2<\/jats:italic> in glutamatergic neurons. PLPPR4 has been identified as a post\u2010synaptic modulator of LPA levels in glutamatergic synapses operating via an uptake mechanism, to control LPA\u2010dependent cortical network hyperexcitability. Using subcellular fractionation experiments, we found that both PLPPR4 and PLPPR3 are co\u2010expressed in adult synaptosomal membranes. Furthermore, flow cytometry experiments in HEK293 cells showed comparable LPA uptake by PLPPR4 and PLPPR3, whereas PLPRR3, but not PLPPR4, induced also uptake of monoacylglycerol, the dephosphorylation product of LPA. We propose that synaptic LPA may be subject to both pre\u2010synaptic and post\u2010synaptic mechanisms of regulation by PLPPRs in addition to LPARs in developing and adult synapses.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16169-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.16169","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T11:45:24Z","timestamp":1720784724000},"page":"3050-3062","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cell type\u2010specific and subcellular expression of phospholipid phosphatase\u2010related proteins to modulate lyso\u2010phosphatidic acid synaptic signaling in the developing and adult <scp>CNS<\/scp>"],"prefix":"10.1111","volume":"168","author":[{"given":"Alexandra","family":"Polyzou","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, School of Health Sciences University of Ioannina  Ioannina Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biochemistry Charit\u00e9 \u2010Universit\u00e4tsmedizin\u2010Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Kroon","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biochemistry Charit\u00e9 \u2010Universit\u00e4tsmedizin\u2010Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Androniki","family":"Kotoula","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, School of Health Sciences 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