Neuropathy target esterase also known as patatin-like phospholipase domain-containing protein 6 (PNPLA6) is a neuropathy target esterase enzyme that in humans is encoded by the PNPLA6gene.[1][2][3][4]
Neuropathy target esterase is a phospholipase that deacetylates intracellular phosphatidylcholine to produce glycerophosphocholine. It is thought to function in neurite outgrowth and process elongation during neuronal differentiation. The protein is anchored to the cytoplasmic face of the endoplasmic reticulum in both neurons and non-neuronal cells.[4]
Neuropathy target esterase is an enzyme with phospholipase B activity: It sequentially hydrolyses both fatty acids from the major membrane lipid phosphatidylcholine, which generates water-soluble glycerophosphocholine.[5][6] In cells of eukaryotes from yeast to humans, NTE is anchored to the cytoplasmic face of the endoplasmic reticulum membrane and is particularly abundant in neurons, the placenta, and the kidney.[7][8][9][10][11] Loss of NTE activity results in abnormally elevated levels of phosphatidylcholine in brain and impairment of the constitutive secretory pathway in neurons.[1][12][13]
Mutations in this gene result in autosomal recessive spastic paraplegia, and the protein is the target for neurodegeneration induced by organophosphorus compounds and chemical warfare agents.[4]
Recessively-inherited mutations in NTE that substantially reduce its catalytic activity cause a rare form of hereditary spastic paraplegia (SPG39), in which distal parts of long spinal axons degenerate leading to limb weakness and paralysis.[15][16]Organophosphate-induced delayed neuropathy— a paralysing syndrome with distal degeneration of long axons— results from poisoning with neuropathic organophosphorus compounds that irreversibly inhibit NTE.[17][18][19][20][21][22]
↑Fernández-Murray JP, McMaster CR (March 2007). "Phosphatidylcholine synthesis and its catabolism by yeast neuropathy target esterase 1". Biochim. Biophys. Acta. 1771 (3): 331–6. doi:10.1016/j.bbalip.2006.04.004. PMID16731034.
↑Li Y, Dinsdale D, Glynn P (March 2003). "Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells". J. Biol. Chem. 278 (10): 8820–5. doi:10.1074/jbc.M210743200. PMID12514188.
↑Zaccheo O, Dinsdale D, Meacock PA, Glynn P (June 2004). "Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells". J. Biol. Chem. 279 (23): 24024–33. doi:10.1074/jbc.M400830200. PMID15044461.
↑Glynn P, Holton JL, Nolan CC, Read DJ, Brown L, Hubbard A, Cavanagh JB (March 1998). "Neuropathy target esterase: immunolocalization to neuronal cell bodies and axons". Neuroscience. 83 (1): 295–302. doi:10.1016/S0306-4522(97)00388-6. PMID9466418.
↑CASIDA JE, ETO M, BARON RL (September 1961). "Biological activity of a trio-cresyl phosphate metabolite". Nature. 191 (4796): 1396–7. doi:10.1038/1911396a0. PMID13877086.
↑Read DJ, Li Y, Chao MV, Cavanagh JB, Glynn P (May 2010). "Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase". Toxicol. Appl. Pharmacol. 245 (1): 108–15. doi:10.1016/j.taap.2010.02.010. PMID20188121.
Further reading
Glynn P (2000). "Neural development and neurodegeneration: two faces of neuropathy target esterase". Prog. Neurobiol. 61 (1): 61–74. doi:10.1016/S0301-0082(99)00043-X. PMID10759065.
Maroni M, Bleecker ML (1986). "Neuropathy target esterase in human lymphocytes and platelets". Journal of applied toxicology : JAT. 6 (1): 1–7. doi:10.1002/jat.2550060102. PMID3958422.
Bertoncin D, Russolo A, Caroldi S, Lotti M (1985). "Neuropathy target esterase in human lymphocytes". Arch. Environ. Health. 40 (3): 139–44. doi:10.1080/00039896.1985.10545905. PMID4026382.
Gurba PE, Richardson RJ (1983). "Partial characterization of neurotoxic esterase of human placenta". Toxicol. Lett. 15 (1): 13–7. doi:10.1016/0378-4274(83)90162-5. PMID6836585.
van Tienhoven M, Atkins J, Li Y, Glynn P (2002). "Human neuropathy target esterase catalyzes hydrolysis of membrane lipids". J. Biol. Chem. 277 (23): 20942–8. doi:10.1074/jbc.M200330200. PMID11927584.
Li Y, Dinsdale D, Glynn P (2003). "Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells". J. Biol. Chem. 278 (10): 8820–5. doi:10.1074/jbc.M210743200. PMID12514188.
Winrow CJ, Hemming ML, Allen DM, et al. (2003). "Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity". Nat. Genet. 33 (4): 477–85. doi:10.1038/ng1131. PMID12640454.
Zaccheo O, Dinsdale D, Meacock PA, Glynn P (2004). "Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells". J. Biol. Chem. 279 (23): 24024–33. doi:10.1074/jbc.M400830200. PMID15044461.
Chang PA; Liu ChY; Chen R; Wu YJ (2006). "Effect of over-expression of neuropathy target esterase on mammalian cell proliferation". Cell Prolif. 39 (5): 429–40. doi:10.1111/j.1365-2184.2006.00399.x. PMID16987144.
Chen R, Chang PA, Long DX, et al. (2007). "Down-regulation of neuropathy target esterase by protein kinase C activation with PMA stimulation". Mol. Cell. Biochem. 302 (1–2): 179–85. doi:10.1007/s11010-007-9439-0. PMID17385009.