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组织非特异性碱性磷酸酶(TNAP),神经元细胞膜脂筏中的关键成分

TNAP, an Essential Player in Membrane Lipid Rafts of Neuronal Cells.

作者信息

Ermonval Myriam, Baychelier Florence, Fonta Caroline

机构信息

Département de Virologie, Institut Pasteur, Unité Des Stratégies Antivirales, F-75015, Paris, France,

出版信息

Subcell Biochem. 2015;76:167-83. doi: 10.1007/978-94-017-7197-9_9.

DOI:10.1007/978-94-017-7197-9_9
PMID:26219712
Abstract

The tissue non-specific alkaline phosphatase (TNAP) is a glycosyl-phosphatidylinositol (GPI) anchored glycoprotein which exists under different forms and is expressed in different tissues. As the other members of the ecto-phosphatase family, TNAP is targeted to membrane lipid rafts. Such micro domains enriched in particular lipids, are involved in cell sorting, are in close contact with the cellular cytoskeleton and play the role of signaling platform. In addition to its location in functional domains, the extracellular orientation of TNAP and the fact this glycoprotein can be shed from plasma membranes, contribute to its different phosphatase activities by acting as a phosphomonoesterase on various soluble substrates (inorganic pyrophosphate -PPi-, pyridoxal phosphate -PLP-, phosphoethanolamine -PEA-), as an ectonucleotidase on nucleotide-phosphate and presumably as a phosphatase able to dephosphorylate phosphoproteins and phospholipids associated to cells or to extra cellular matrix. More and more data accumulate on an involvement of the brain TNAP both in physiological and pathological situations. This review will summarize what is known and expected from the TNAP localization in lipid rafts with a particular emphasis on the role of a neuronal microenvironment on its potential function in the central nervous system.

摘要

组织非特异性碱性磷酸酶(TNAP)是一种糖基磷脂酰肌醇(GPI)锚定糖蛋白,以不同形式存在并在不同组织中表达。作为胞外磷酸酶家族的其他成员,TNAP定位于膜脂筏。这种富含特定脂质的微结构域参与细胞分选,与细胞骨架紧密接触并发挥信号平台的作用。除了其在功能结构域中的定位外,TNAP的细胞外取向以及该糖蛋白可从质膜脱落这一事实,通过对各种可溶性底物(无机焦磷酸-PPi-、磷酸吡哆醛-PLP-、磷酸乙醇胺-PEA-)起磷酸单酯酶作用、对核苷酸磷酸起胞外核苷酸酶作用以及大概作为一种能够使与细胞或细胞外基质相关的磷蛋白和磷脂去磷酸化的磷酸酶,从而有助于其不同的磷酸酶活性。越来越多的数据表明,脑TNAP在生理和病理情况下均有参与。本综述将总结关于TNAP在脂筏中的定位已知和预期的情况,特别强调神经元微环境对其在中枢神经系统中潜在功能的作用。

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引用本文的文献

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The structural pathology for hypophosphatasia caused by malfunctional tissue non-specific alkaline phosphatase.由功能失调的组织非特异性碱性磷酸酶引起的低磷酸酯酶症的结构病理学。
Nat Commun. 2023 Jul 8;14(1):4048. doi: 10.1038/s41467-023-39833-3.
2
(Patho)Physiology of Glycosylphosphatidylinositol-Anchored Proteins I: Localization at Plasma Membranes and Extracellular Compartments.糖基磷脂酰肌醇锚定蛋白的病理生理学 I:在质膜和细胞外隔室中的定位。
Biomolecules. 2023 May 18;13(5):855. doi: 10.3390/biom13050855.
3
Investigation of alpl expression and Tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development.
研究表明,斑马鱼中 alpL 表达和 Tnap 活性在骨骼和神经元发育过程中具有保守功能。
Sci Rep. 2020 Aug 7;10(1):13321. doi: 10.1038/s41598-020-70152-5.
4
Lipid composition modulates ATP hydrolysis and calcium phosphate mineral propagation by TNAP-harboring proteoliposomes.脂质组成通过含有 TNAP 的蛋白脂质体调节 ATP 水解和磷酸钙矿化的传播。
Arch Biochem Biophys. 2020 Sep 30;691:108482. doi: 10.1016/j.abb.2020.108482. Epub 2020 Jul 22.