Mammalian Glycerophosphodiester Phosphodiesterases

Yanaka, Noriyuki

doi:10.1271/bbb.70062

Cited by 65 publications

(70 citation statements)

References 51 publications

(59 reference statements)

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“…GP-PDEs are widely found in prokaryotes and eukaryotes, although their distinct physiological roles remain unclear, particularly in eukaryotes (5,6). Mammalian GP-PDEs have more selective substrate specificities toward GPs, which prompts us to assume that their enzymatic activities are mainly devoted to modulate GroPIns and/or GroPCho concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…GPs are produced via phospholipase A 1 and phospholipase A 2 activities, and they are degraded by GP phosphodiesterases (GP-PDEs) (1)(2)(3)(4). Six mammalian GP-PDEs were previously isolated, and investigations have been carried out to explore their physiological significance (5,6). In renal cells, GDE2 contributes to osmotic regulation as a GroPCho phosphodiesterase, which is supported by increasing evidence that GroPCho acts as an organic osmolyte (7)(8)(9).…”

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confidence: 99%

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New Members of the Mammalian Glycerophosphodiester Phosphodiesterase Family

Ohshima

Kudo

Yamashita

et al. 2015

Journal of Biological Chemistry

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Background:The known mammalian glycerophosphodiester phosphodiesterases hydrolyze glycerophosphodiesters. Results: New members of the glycerophosphodiester phosphodiesterase family, GDE4 and GDE7, cannot hydrolyze glycerophosphodiesters but show lysophospholipase D activity. Conclusion: GDE4 and GDE7 can hydrolyze 1-acyl-lyso-PC and lyso-PAF to produce 1-acyl-lysophosphatidic acid (LPA) and alkyl-LPA, respectively. Significance: The mammalian glycerophosphodiester phosphodiesterase family may have a new function in LPA signaling.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

New Members of the Mammalian Glycerophosphodiester Phosphodiesterase Family

Ohshima

Kudo

Yamashita

et al. 2015

Journal of Biological Chemistry

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“…Analysis of the 270-bp differential display sequence confirmed 99% homology to the GPCPD1, GPC phosphodiesterase (PDE) GDE1 (Saccharomyces cerevisiae) homolog gene on chromosome 20p13. Glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae) (GPCPD1) is included as a member of the mammalian glycerophosphodiesterase (GDE) family (20), specifically GDE5, because of the presence of a GDE domain at the N terminus. Unlike other members of the GDE family, GDE5/GPCPD1/EDI3 (EDI3 for simplicity) contains no transmembrane domains, but is instead localized to the cytoplasm (20,21).…”

Section: Edi3 Predicts Metastasis In Endometrial and Ovarian Cancermentioning

confidence: 99%

“…Glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae) (GPCPD1) is included as a member of the mammalian glycerophosphodiesterase (GDE) family (20), specifically GDE5, because of the presence of a GDE domain at the N terminus. Unlike other members of the GDE family, GDE5/GPCPD1/EDI3 (EDI3 for simplicity) contains no transmembrane domains, but is instead localized to the cytoplasm (20,21). A recent study illustrated that the preferred substrate for EDI3 is GPC, and that in mice the enzyme may play an important role in skeletal muscle development (21).…”

Section: Edi3 Predicts Metastasis In Endometrial and Ovarian Cancermentioning

confidence: 99%

Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis

Stewart

Marchan

Lesjak

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

126

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Metastasis from primary tumors remains a major problem for tumor therapy. In the search for markers of metastasis and more effective therapies, the tumor metabolome is relevant because of its importance to the malignant phenotype and metastatic capacity of tumor cells. Altered choline metabolism is a hallmark of cancer. More specifically, a decreased glycerophosphocholine (GPC) to phosphocholine (PC) ratio was reported in breast, ovarian, and prostate cancers. Improved strategies to exploit this altered choline metabolism are therefore required. However, the critical enzyme cleaving GPC to produce choline, the initial step in the pathway controlling the GPC/PC ratio, remained unknown. In the present work, we have identified the enzyme, here named EDI3 (endometrial differential 3). Purified recombinant EDI3 protein cleaves GPC to form glycerol-3-phosphate and choline. Silencing EDI3 in MCF-7 cells decreased this enzymatic activity, increased the intracellular GPC/PC ratio, and decreased downstream lipid metabolites. Downregulating EDI3 activity inhibited cell migration via disruption of the PKCα signaling pathway, with stable overexpression of EDI3 showing the opposite effect. EDI3 was originally identified in our screening study comparing mRNA levels in metastasizing and nonmetastasizing endometrial carcinomas. Both Kaplan-Meier and multivariate analyses revealed a negative association between high EDI3 expression and relapse-free survival time in both endometrial (P < 0.001) and ovarian (P = 0.029) cancers. Overall, we have identified EDI3, a key enzyme controlling GPC and choline metabolism. Because inhibition of EDI3 activity corrects the GPC/PC ratio and decreases the migration capacity of tumor cells, it represents a possible target for therapeutic intervention.

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“…One candidate enzyme class is the glycerophosphodiester phosphodiesterases (GDEs), which hydrolyze the phosphodiester bond of glycerophosphodiesters to yield glycerol phosphate and an alcohol (16). Enzymes containing this GDE domain have been shown to play roles in glycerophospholipid metabolism in yeast and bacteria (17).…”

Section: Methodsmentioning

confidence: 99%

Anandamide Biosynthesis Catalyzed by the Phosphodiesterase GDE1 and Detection of Glycerophospho-N-acyl Ethanolamine Precursors in Mouse Brain

Simón

Cravatt

2008

Journal of Biological Chemistry

214

133

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Anandamide (AEA) is an endogenous ligand of cannabinoid receptors and a well characterized mediator of many physiological processes including inflammation, pain, and appetite. The biosynthetic pathway(s) for anandamide and its N-acyl ethanolamine (NAE) congeners remain enigmatic. Previously, we proposed an enzymatic route for producing NAEs that involves the double-O-deacylation of N-acyl phosphatidylethanolamines (NAPEs) by ␣/␤-hydrolase 4 (ABDH4 or Abh4) to form glycerophospho (GP)-NAEs, followed by conversion of these intermediates to NAEs by an unidentified phosphodiesterase. Here, we report the detection and measurement of GP-NAEs, including the anandamide precursor glycerophospho-N-arachidonoylethanolamine (GP-NArE), as endogenous constituents of mouse brain tissue. Inhibition of the phosphodiesterase-mediated degradation of GP-NAEs ex vivo resulted in a striking accumulation of these lipids in brain extracts, suggesting a rapid endogenous flux through this pathway. Furthermore, we identify the glycerophosphodiesterase GDE1, also known as MIR16, as a broadly expressed membrane enzyme with robust GP-NAE phosphodiesterase activity. Together, these data provide evidence for a multistep pathway for the production of anandamide in the nervous system by the sequential actions of Abh4 and GDE1.

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Mammalian Glycerophosphodiester Phosphodiesterases

Cited by 65 publications

References 51 publications

New Members of the Mammalian Glycerophosphodiester Phosphodiesterase Family

New Members of the Mammalian Glycerophosphodiester Phosphodiesterase Family

Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis

Anandamide Biosynthesis Catalyzed by the Phosphodiesterase GDE1 and Detection of Glycerophospho-N-acyl Ethanolamine Precursors in Mouse Brain

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