PRIP (Phospholipase C-related but Catalytically Inactive Protein) Inhibits Exocytosis by Direct Interactions with Syntaxin 1 and SNAP-25 through Its C2 Domain

Zhao, Zhihui; Takeuchi, Hiroshi; Gao, Jing; Wang, Da Guang; James, Declan J.; Martin, Thomas F.J.; Hirata, Masato

doi:10.1074/jbc.m112.419317

Cited by 19 publications

(24 citation statements)

References 52 publications

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“…gesting that the higher secretion of gonadotropin that was observed does not occur through a feedback loop in the HPG axis (25). These results and our previous studies suggest that PRIPs are negatively involved in exocytosis in the pituitary gland, which leads to the secretion of peptide hormones (12,13,25).…”

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confidence: 73%

“…They were named because they lacked catalytic activity, despite having a domain organization that is similar to phospholipase C-␦1, which includes a pleckstrin homology (PH) domain, EF-hand motifs, catalytic X and Y, and C2 domains (6, 7). Several interacting partners have been identified for PRIPs, including ␥-aminobutyric acid type A (GABA A ) receptor-associated protein (8), the ␤ subunit of the GABA A receptor (9), the catalytic subunits of protein phosphatase 1␣ and 2A (9, 10), the phosphorylated form of Akt (11), and SNARE proteins (12,13), in addition to Ins(1,4,5)P 3 and phosphatidylinositol 4,5-bisphosphate (14,15). The discovery of these binding partners led to the identification of the involvement of PRIPs in Ins(1,4,5)P 3 / Ca 2ϩ signaling (14,16), GABA A receptor signaling (17-19), protein dephosphorylation (20, 21), and exocytosis (12, 13).…”

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confidence: 99%

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Phospholipase C-related but catalytically inactive proteins regulate ovarian follicle development

Matsuda

Hirata

2017

Journal of Biological Chemistry

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Phospholipase C-related but catalytically inactive proteins PRIP-1 and -2 are inositol-1,4,5-trisphosphate binding proteins that are encoded by independent genes. Ablation of the genes in mice impairs female fertility, which is manifested by fewer pregnancies, a decreased number of pups, and the decreased and increased secretion of gonadal steroids and gonadotropins, respectively. We investigated the involvement of the PRIPs in fertility, focusing on the ovaries of and double-knock-out (DKO) mice. Multiple cystic follicles were observed in DKO ovaries, and a superovulation assay showed a markedly decreased number of ovulated oocytes. Cumulus-oocyte complexes showed normal expansion, and artificial gonadotropin stimulation regulated the ovulation-related genes in a normal fashion, suggesting that the ovulation itself was probably normal. A histological analysis showed atresia in fewer follicles of the DKO ovaries, particularly in the secondary follicle stages. The expression of luteinizing hormone receptor (LHR) was aberrantly higher in developing follicles, and the phosphorylation of extracellular signal-regulated protein kinase, a downstream target of LH-LHR signaling, was higher in DKO granulosa cells. This suggests that the up-regulation of LH-LHR signaling is the cause of impaired follicle development. The serum estradiol level was lower, but estradiol production was unchanged in the DKO ovaries. These results suggest that PRIPs are positively involved in the development of follicles via their regulation of LH-LHR signaling and estradiol secretion. Female DKO mice had higher serum levels of insulin, testosterone, and uncarboxylated osteocalcin, which, together with reduced fertility, are reminiscent of polycystic ovary syndrome in humans.

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confidence: 73%

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confidence: 99%

Phospholipase C-related but catalytically inactive proteins regulate ovarian follicle development

Matsuda

Hirata

2017

Journal of Biological Chemistry

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“…Phospholipase C Like 1, inactive (PLCL1) was up-regulated in response to RIF exposure ( Fig 5D). PLCL1 is involved in the inhibition of exocytosis through its interactions with syntaxin 1 and SNAP-25 [40].…”

Section: Enriched Canonical Pathways Following Exposure To Pbdes Citmentioning

confidence: 99%

Transcriptomic profiling of PBDE-exposed HepaRG cells unveils critical lncRNA- PCG pairs involved in intermediary metabolism

Zhang

Kelly

et al. 2020

PLoS ONE

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Polybrominated diphenyl ethers (PBDEs) were formally used as flame-retardants and are chemically stable, lipophlic persistent organic pollutants which are known to bioaccumulate in humans. Although its toxicities are well characterized, little is known about the changes in transcriptional regulation caused by PBDE exposure. Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of transcriptional and translational processes. It is hypothesized that lncRNAs can regulate nearby protein-coding genes (PCGs) and changes in the transcription of lncRNAs may act in cis to perturb gene expression of its neighboring PCGs. The goals of this study were to 1) characterize PCGs and lncRNAs that are differentially regulated from exposure to PBDEs; 2) identify PCG-lncRNA pairs through genome annotation and predictive binding tools; and 3) determine enriched canonical pathways caused by differentially expressed lncRNA-PCGs pairs. HepaRG cells, which are humanderived hepatic cells that accurately represent gene expression profiles of human liver tissue, were exposed to BDE-47 and BDE-99 at a dose of 25 μM for 24 hours. Differentially expressed lncRNA-PCG pairs were identified through DESeq2 and HOMER; significant canonical pathways were determined through Ingenuity Pathway Analysis (IPA). LncTar was used to predict the binding of 19 lncRNA-PCG pairs with known roles in drug-processing pathways. Genome annotation revealed that the majority of the differentially expressed lncRNAs map to PCG introns. PBDEs regulated overlapping pathways with PXR and CAR such as protein ubiqutination pathway and peroxisome proliferator-activated receptor alpharetinoid X receptor alpha (PPARα-RXRα) activation but also regulate distinctive pathways involved in intermediary metabolism. PBDEs uniquely down-regulated GDP-L-fucose biosynthesis, suggesting its role in modifying important pathways involved in intermediary metabolism such as carbohydrate and lipid metabolism. In conclusion, we provide strong evidence that PBDEs regulate both PCGs and lncRNAs in a PXR/CAR ligand-dependent and independent manner.

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“…Later, an isoform with relatively broad tissue distribution, including the brain, was reported, comprising PRIP‐1 and ‐2 [Kikuno et al, ; Otsuki et al, ; Uji et al, ]. Subsequent studies revealed that there are a number of binding partners, including GABARAP [γ‐aminobutyric acid type A (GABA A ) receptor‐associated protein] [Kanematsu et al, ], the catalytic subunit of protein phosphatase 1 and 2A [Yoshimura et al, ; Terunuma et al, ; Kanematsu et al, ; Yanagihori et al, ; Gao et al, ], the phosphorylated (active) form of Akt [Fujii et al, ], the β subunits of the GABA A receptor [Terunuma et al, ; Kanematsu et al, ; Kanematsu et al, ] and SNARE proteins, syntaxin 1 and SNAP‐25 [Gao et al, ; Zhang et al, ], in addition to inositol 1,4,5‐trisphosphate.…”

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confidence: 99%

“…We further generated PRIP gene‐deficient mice, in each subtype or both and performed analyses of the phenotypes for information regarding the physiological functions mainly using PRIP‐1 and ‐2 double knock out (KO) mice, since binding properties to some of the above‐mentioned molecules provided little difference between PRIP‐1 and ‐2. Binding partners with known functions helped the analyses: inositol 1,4,5‐trisphosphate‐mediated Ca 2+ signaling [Takeuchi et al, ; Harada et al, ], GABA A receptor signaling [Kanematsu et al, , , ; Terunuma et al, ; Mizokami et al, , ; Fujii et al, ], phospho‐regulation through phosphatase swapping [Sugiyama et al, ] and negative regulation of exocytosis [Gao et al, ; Zhang et al, ].…”

mentioning

confidence: 99%

Involvement of PRIP (Phospholipase C‐Related But Catalytically Inactive Protein) in BMP‐Induced Smad Signaling in Osteoblast Differentiation

Kotani

Matsuda

Murakami

et al. 2015

J of Cellular Biochemistry

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Phospholipase C-related but catalytically inactive protein (PRIP) was first isolated as an inositol 1,4,5-trisphosphate binding protein. We generated PRIP gene-deficient mice which exhibited the increased bone mineral density and trabecular bone volume, indicating that PRIP is implicated in the regulation of bone properties. In this study, we investigated the possible mechanisms by which PRIP plays a role in bone morphogenetic protein (BMP) signaling, by analyzing the culture of primary cells isolated from calvaria of two genotypes, the wild type and a mutant. In the mutant culture, enhanced osteoblast differentiation was observed by measuring alkaline phosphatase staining and activity. The promoter activity of Id1 gene, responding immediately to BMP, was also more increased. Smad1/5 phosphorylation in response to BMP showed an enhanced peak and was more persistent in mutant cells, but the dephosphorylation process was not different between the two genotypes. The luciferase assay using calvaria cells transfected with the Smad1 mutated as a constitutive active form showed increased transcriptional activity at similar levels between the genotypes. The expression of BMP receptors was not different between the genotypes. BMP-induced phosphorylation of Smad1/5 was robustly decreased in wild type cells, but not in mutant cells, by pretreatment with DB867, an inhibitor of methyltransferase of inhibitory Smad6. Furthermore, BMP-induced translocation of Smad6 from nucleus to cytosol was not much observed in PRIP-deficient cells. These results indicate that PRIP is implicated in BMP-induced osteoblast differentiation by the negative regulation of Smad phosphorylation, through the methylation of inhibitory Smad6.

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PRIP (Phospholipase C-related but Catalytically Inactive Protein) Inhibits Exocytosis by Direct Interactions with Syntaxin 1 and SNAP-25 through Its C2 Domain

Cited by 19 publications

References 52 publications

Phospholipase C-related but catalytically inactive proteins regulate ovarian follicle development

Phospholipase C-related but catalytically inactive proteins regulate ovarian follicle development

Transcriptomic profiling of PBDE-exposed HepaRG cells unveils critical lncRNA- PCG pairs involved in intermediary metabolism

Involvement of PRIP (Phospholipase C‐Related But Catalytically Inactive Protein) in BMP‐Induced Smad Signaling in Osteoblast Differentiation

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