Ask about this productRelated genes to: PAP2D antibody
- Gene:
- PLPPR5 NIH gene
- Name:
- phospholipid phosphatase related 5
- Previous symbol:
- -
- Synonyms:
- PAP2D, PAP2, LPPR5, PRG5
- Chromosome:
- 1p21.3
- Locus Type:
- gene with protein product
- Date approved:
- 2015-10-14
- Date modifiied:
- 2015-10-14
Related products to: PAP2D antibody
Related articles to: PAP2D antibody
- Major depressive disorder (MDD) is a highly prevalent and disabling neuropsychiatric condition, its underlying molecular mechanisms remain incompletely understood. This study aimed to systematically characterize proteomic alterations in the prefrontal cortex associated with depression-like behaviors induced by chronic stress. Depression-like behaviors in mice were evaluated using standardized behavioral tests and confirmed by Digital Western blotting. Quantitative proteomic analysis of prefrontal cortex tissues was performed to compare chronic social defeat stress (CSDS) and control groups, identifying differentially expressed proteins (DEPs). These DEPs were subsequently subjected to bioinformatic analyses, including Gene Ontology (GO) enrichment and construction of protein-protein interaction (PPI) networks. Key DEPs were further validated by parallel reaction monitoring (PRM) and Western blotting. We found that CSDS mice displayed robust depression-like phenotypes, including decreased sucrose preference and increased immobility. Western blot analysis confirmed the dysregulation of ER stress markers, proinflammatory factors, and proteins related to synaptic plasticity. Proteomic analysis identified 95 differentially expressed proteins, with GO enrichment revealing predominant associations with gene regulation, mitochondrial, metabolic, and synaptic function. PPI network analysis highlighted hub proteins involved in mitochondrial, endoplasmic reticulum, and synaptic regulation. PRM and Western blot validation confirmed dysregulation in four functional modules: 1) Mitochondrial function (Mrpl17, Mrpl41)；2) Signal transduction (Rigi, Pbrm1, Plppr5, Glyr1)；3) Metabolic regulation(Pmvk, Rpl13a, Ubtd2, Tmem63b)；4) Synaptic plasticity (Kif21b, Klc4, Lama2, Col4a2). Our results demonstrate that chronic stress disrupts prefrontal cortical pathways that govern gene regulation, mitochondrial metabolism, and synaptic function, suggesting their concerted contribution to the pathophysiology of depression. - Source: PubMed
Publication date: 2026/02/27
Zhang YiLi LeiZhang XiaoweiXu JiyiKan WeijingWang TianyiDu Jing - 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-characterized receptors, atypical regulators of LPA signaling have also been suggested, including phospholipid phosphatase-related proteins (PLPPRs). PLPPRs have been mostly studied in the developing brain where they control LPA-dependent 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 Plppr2,4 and 5 were consistent with previous studies, whereas Plppr3 and Plppr1 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-specific expression at the single cell level, we developed a bioinformatic tool to analyze recent single-cell RNA-sequencing data in the cerebral cortex and hippocampus of adult mice. Our analysis revealed a widespread but also selective adult neuron-type expression with higher expression levels of Plppr3, Plppr1, and Plppr5 in GABAergic and Plppr4 and Plppr2 in glutamatergic neurons. PLPPR4 has been identified as a post-synaptic modulator of LPA levels in glutamatergic synapses operating via an uptake mechanism, to control LPA-dependent cortical network hyperexcitability. Using subcellular fractionation experiments, we found that both PLPPR4 and PLPPR3 are co-expressed 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-synaptic and post-synaptic mechanisms of regulation by PLPPRs in addition to LPARs in developing and adult synapses. - Source: PubMed
Publication date: 2024/07/12
Polyzou AlexandraFuchs JoachimKroon CristinaKotoula AndronikiDelis FoteiniTurko PaulAntoniou KaterinaEickholt BrittaLeondaritis George - Mice with inactivation of the Plppr5 gene (Plppr5-/-) had aggravated hypoxic-ischemic damage and partially weakened neuroprotection of melatonin (a mitochondrial targeted antioxidant), suggesting that abnormal mitochondrial homeostasis contributes to neurological abnormalities in these mice. We examined the hypothesis that Plppr5 inactivation disturbs mitochondrial homeostasis, which may cause long-term adverse consequences on behavior and cognition. We studied the long-term effects of Plppr5 knockout (KO) in both wild-type (WT) and Plppr5-null mice using a combination of neurobehavior, cognition, and standard cellular glutamate-induced excitotoxicity techniques. The change in mitochondrial membrane potential was determined by detecting MitoTracker Green FM and MitoTracker Red CMXROS with a Gallios flow cytometer. Our results suggest that Plppr5 gene knockout aggravated the impairment of exploratory behavior (open field test) and memory (novel object recognition and passive avoidance tests) in Plppr5-null mice following juvenile seizures. Furthermore, Plppr5 gene silencing aggravated the decrease in the cell survival rate of HT22 cells treated with glutamate for 24 h and further resulted in a decrease in superoxide dismutase (SOD) levels and the ratio of active mitochondria and a parallel increase in the reactive oxygen species (ROS) content. Interestingly, silencing the Plppr5 gene alone in vitro is sufficient to reduce the cell survival rate, aggravate oxidative stress damage, reduce the proportion of surviving mitochondria, and upregulate mitophagy activity. In summary, the present data reveal the first direct link between Plppr5 KO and neurobehavioral and cognitive impairment following juvenile seizures and provide a potential mechanistic explanation for the adverse consequences. Given that silencing the Plppr5 gene is sufficient to upregulate mitophagy activity and aggravate oxidative stress neuronal damage, our results suggest that Plppr5 substrates and/or mitophagy-based treatments may provide valuable new targets for the treatment of developmental convulsive brain injury. - Source: PubMed
Publication date: 2022/05/20
Wang DandanLiu YueyingZhao DongjingJin MeifangLi LiliNi Hong - Hypoxia-ischemia (HI) is the most common acute brain threat in neonates and a leading cause of neurodevelopmental impairment. Exploring the new molecular mechanism of HI brain injury has important clinical translational significance for the next clinical intervention research. Lipid phosphatase-related proteins (PLPPRs) are regulators of mitochondrial membrane integrity and energy metabolism. We recently found that knockout exacerbated HI impairment in some aspects and partially attenuated the neuroprotective effects of melatonin, suggesting that may be a novel intervention target for HI. The present study aimed to determine the long-term effects of gene knockout of on HI brain injury, focusing on the neuronal excitability phenotype, and to determine the effect of gene silencing on neuronal zinc metabolism and mitochondrial function . 10-day-old wild type (WT) mice and -deficient ( ) mice were subjected to hypoxia-ischemia. Lesion volumes and HI-induced neuroexcitotoxic phenotypes were quantified together with ZnT1 protein expression in hippocampus. In addition, HT22 (mouse hippocampal neuronal cells) cell model was established by oxygen-glucose deprivation/reoxygenation (OGD/R) treatment and was treated with medium containing LV-sh_ or control virus. Mitochondrial oxidative stress indicator ROS, mitochondrial ZnT1 protein expression and zinc ion content were detected. - Source: PubMed
Publication date: 2022/03/24
Sun YuxiaoJin Mei-FangLi LiliLiu YueyingWang DandanNi Hong - [This corrects the article DOI: 10.3389/fendo.2021.598788.]. - Source: PubMed
Publication date: 2022/03/14
Sun YuxiaoMa LiyaJin MeifangZheng YuqinWang DandanNi Hong