Biology:Neuropathy target esterase
 Generic protein structure example |
Neuropathy target esterase, also known as patatin-like phospholipase domain-containing protein 6 (PNPLA6), is an esterase enzyme that in humans is encoded by the PNPLA6 gene.[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]
Function
Neuropathy target esterase is an enzyme with phospholipase B activity: it sequentially hydrolyses both fatty acids from the major membrane lipid phosphatidylcholine, generating water-soluble glycerophosphocholine.[5][6] In eukaryotic cells, NTE is anchored to the cytoplasmic face of the endoplasmic reticulum membrane. In mammals, it 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 the brain and impairment of the constitutive secretory pathway in neurons.[1][12][13]
In the kidney, the expression of neuropathy target esterase is regulated by TonEBP as part of osmolyte production when the kidney produces concentrated urine.[14]
Clinical significance
Mutations in this gene result in autosomal-recessive spastic paraplegia. The protein is also 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]
References
- ↑ 1.0 1.1 "Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man". Biochem J. 332 ( Pt 1) (Pt 1): 1–4. Aug 1998. doi:10.1042/bj3320001. PMID 9576844.
- ↑ "Characterization of the human patatin-like phospholipase family". J Lipid Res 47 (9): 1940–9. Aug 2006. doi:10.1194/jlr.M600185-JLR200. PMID 16799181.
- ↑ "Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions". J Lipid Res 50 Suppl (Supplement): S63–8. Apr 2009. doi:10.1194/jlr.R800082-JLR200. PMID 19029121.
- ↑ 4.0 4.1 4.2 "Entrez Gene: PNPLA6 patatin-like phospholipase domain containing 6". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10908.
- ↑ Glynn P (September 2005). "Neuropathy target esterase and phospholipid deacylation". Biochim. Biophys. Acta 1736 (2): 87–93. doi:10.1016/j.bbalip.2005.08.002. PMID 16137924.
- ↑ "Phosphatidylcholine synthesis and its catabolism by yeast neuropathy target esterase 1". Biochim. Biophys. Acta 1771 (3): 331–6. March 2007. doi:10.1016/j.bbalip.2006.04.004. PMID 16731034.
- ↑ "Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells". J. Biol. Chem. 278 (10): 8820–5. March 2003. doi:10.1074/jbc.M210743200. PMID 12514188.
- ↑ "Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells". J. Biol. Chem. 279 (23): 24024–33. June 2004. doi:10.1074/jbc.M400830200. PMID 15044461.
- ↑ "Neuropathy target esterase: immunolocalization to neuronal cell bodies and axons". Neuroscience 83 (1): 295–302. March 1998. doi:10.1016/S0306-4522(97)00388-6. PMID 9466418.
- ↑ "Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice". Mol. Cell. Biol. 24 (4): 1667–79. February 2004. doi:10.1128/mcb.24.4.1667-1679.2004. PMID 14749382.
- ↑ "Neuropathy target esterase catalyzes osmoprotective renal synthesis of glycerophosphocholine in response to high NaCl". Proc. Natl. Acad. Sci. U.S.A. 103 (41): 15260–5. October 2006. doi:10.1073/pnas.0607133103. PMID 17015841. Bibcode: 2006PNAS..10315260G.
- ↑ "Loss of Swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila". J. Neurosci. 25 (11): 2865–73. March 2005. doi:10.1523/JNEUROSCI.5097-04.2005. PMID 15772346.
- ↑ "Neuropathy target esterase is required for adult vertebrate axon maintenance". J. Neurosci. 29 (37): 11594–600. September 2009. doi:10.1523/JNEUROSCI.3007-09.2009. PMID 19759306.
- ↑ Gallazzini, M.; Burg, M. B. (2009). "What's New About Osmotic Regulation of Glycerophosphocholine". Physiology 24 (4): 245–249. doi:10.1152/physiol.00009.2009. PMID 19675355.
- ↑ "Neuropathy target esterase gene mutations cause motor neuron disease". Am. J. Hum. Genet. 82 (3): 780–5. March 2008. doi:10.1016/j.ajhg.2007.12.018. PMID 18313024.
- ↑ "Motor neuron disease due to neuropathy target esterase gene mutation: clinical features of the index families". Muscle Nerve 43 (1): 19–25. January 2011. doi:10.1002/mus.21777. PMID 21171093.
- ↑ "Organophosphate-induced delayed polyneuropathy". Toxicol Rev 24 (1): 37–49. 2005. doi:10.2165/00139709-200524010-00003. PMID 16042503.
- ↑ CAVANAGH JB (August 1954). "The toxic effects of triortho-cresyl phosphate on the nervous system; an experimental study in hens". J. Neurol. Neurosurg. Psychiatry 17 (3): 163–72. doi:10.1136/jnnp.17.3.163. PMID 13192490.
- ↑ "Biological activity of a trio-cresyl phosphate metabolite". Nature 191 (4796): 1396–7. September 1961. doi:10.1038/1911396a0. PMID 13877086. Bibcode: 1961Natur.191.1396C.
- ↑ Johnson MK (October 1969). "The delayed neurotoxic effect of some organophosphorus compounds. Identification of the phosphorylation site as an esterase". Biochem. J. 114 (4): 711–7. doi:10.1042/bj1140711. PMID 4310054.
- ↑ "Synthesis and characterization of a biotinylated organophosphorus ester for detection and affinity purification of a brain serine esterase: neuropathy target esterase". Biochem. J. 301 ( Pt 2) (2): 551–6. July 1994. doi:10.1042/bj3010551. PMID 8043002.
- ↑ "Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase". Toxicol. Appl. Pharmacol. 245 (1): 108–15. May 2010. doi:10.1016/j.taap.2010.02.010. PMID 20188121.
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. PMID 10759065.
- "Neuropathy target esterase in human lymphocytes and platelets.". Journal of Applied Toxicology 6 (1): 1–7. 1986. doi:10.1002/jat.2550060102. PMID 3958422.
- "Neuropathy target esterase in human lymphocytes.". Arch. Environ. Health 40 (3): 139–44. 1985. doi:10.1080/00039896.1985.10545905. PMID 4026382.
- "Partial characterization of neurotoxic esterase of human placenta.". Toxicol. Lett. 15 (1): 13–7. 1983. doi:10.1016/0378-4274(83)90162-5. PMID 6836585. https://deepblue.lib.umich.edu/bitstream/2027.42/25337/1/0000783.pdf.
- "Human neuropathy target esterase catalyzes hydrolysis of membrane lipids.". J. Biol. Chem. 277 (23): 20942–8. 2002. doi:10.1074/jbc.M200330200. PMID 11927584.
- Strausberg RL; Feingold EA; Grouse LH; Derge, JG; Klausner, RD; Collins, FS; Wagner, L; Shenmen, CM et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells". J. Biol. Chem. 278 (10): 8820–5. 2003. doi:10.1074/jbc.M210743200. PMID 12514188.
- Winrow CJ; Hemming ML; Allen DM; Quistad, Gary B.; Casida, John E.; Barlow, Carrolee (2003). "Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity". Nat. Genet. 33 (4): 477–85. doi:10.1038/ng1131. PMID 12640454.
- "Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells". J. Biol. Chem. 279 (23): 24024–33. 2004. doi:10.1074/jbc.M400830200. PMID 15044461.
- Beausoleil SA; Jedrychowski M; Schwartz D; Elias, JE; Villén, J; Li, J; Cohn, MA; Cantley, LC et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMID 15302935. Bibcode: 2004PNAS..10112130B.
- Chang PA; Wu YJ; Chen R; Li, Ming; Li, Wei; Qin, Qi-Lian (2005). "Inhibition of neuropathy target esterase expressing by antisense RNA does not affect neural differentiation in human neuroblastoma (SK-N-SH) cell line". Mol. Cell. Biochem. 272 (1–2): 47–54. doi:10.1007/s11010-005-6753-2. PMID 16010971.
- "Reduction of neuropathy target esterase does not affect neuronal differentiation, but moderate expression induces neuronal differentiation in human neuroblastoma (SK-N-SH) cell line". Brain Res. Mol. Brain Res. 141 (1): 30–8. 2006. doi:10.1016/j.molbrainres.2005.07.012. PMID 16122834.
- Kimura K; Wakamatsu A; Suzuki Y; Ota, T; Nishikawa, T; Yamashita, R; Yamamoto, J; Sekine, M et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMID 16344560.
- 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. PMID 16987144.
- Chen R; Chang PA; Long DX; Yang, Lin; Wu, Yi-Jun (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. PMID 17385009.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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