// Workers AI · dad joke modeWhat did neuropathy target esterase say? "I'm a little numb to relationships.
(Redirected from PNPLA6)
| PNPLA6 | |||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||||||||||||||||||||
| Aliases | PNPLA6, BNHS, NTE, NTEMND, SPG39, iPLA2delta, sws, LNMS, OMCS, patatin like phospholipase domain containing 6 | ||||||||||||||||||||||||||||||
| External IDs | OMIM: 603197; MGI: 1354723; HomoloGene: 21333; GeneCards: PNPLA6; OMA:PNPLA6 - orthologs | ||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||
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.[5][6][7][8]
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.[8]
Function
[edit]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.[9][10] 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.[11][12][13][14][15] Loss of NTE activity results in abnormally-elevated levels of phosphatidylcholine in the brain and impairment of the constitutive secretory pathway in neurons.[5][16][17]
In the kidney, the expression of neuropathy target esterase is regulated by TonEBP as part of osmolyte production when the kidney produces concentrated urine.[18]
Clinical significance
[edit]Recessively-inherited mutations in NTE that substantially reduce 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.[19][20] Organophosphate-induced delayed neuropathy— a paralysing syndrome with distal degeneration of long axons— results from poisoning with toxic organophosphorus compounds that irreversibly inhibit NTE.[21][22][23][24][25][26]
References
[edit]- 1 2 3 GRCh38: Ensembl release 89: ENSG00000032444 – Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000004565 – Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- 1 2 Lush MJ, Li Y, Read DJ, Willis AC, Glynn P (August 1998). "Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man". The Biochemical Journal. 332. ( Pt 1) (Pt 1): 1–4. doi:10.1042/bj3320001. PMC 1219444. PMID 9576844.
- ↑ Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ (August 2006). "Characterization of the human patatin-like phospholipase family". Journal of Lipid Research. 47 (9): 1940–1949. doi:10.1194/jlr.M600185-JLR200. PMID 16799181.
- ↑ Kienesberger PC, Oberer M, Lass A, Zechner R (April 2009). "Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions". Journal of Lipid Research. 50 Suppl (Supplement): S63–8. Bibcode:2009JLipR..50S..63K. doi:10.1194/jlr.R800082-JLR200. PMC 2674697. PMID 19029121.
- 1 2 "Entrez Gene: PNPLA6 patatin-like phospholipase domain containing 6".
- ↑ Glynn P (September 2005). "Neuropathy target esterase and phospholipid deacylation". Biochimica et Biophysica Acta. 1736 (2): 87–93. doi:10.1016/j.bbalip.2005.08.002. PMID 16137924.
- ↑ Fernández-Murray JP, McMaster CR (March 2007). "Phosphatidylcholine synthesis and its catabolism by yeast neuropathy target esterase 1". Biochimica et Biophysica Acta. 1771 (3): 331–336. doi:10.1016/j.bbalip.2006.04.004. PMID 16731034.
- ↑ Li Y, Dinsdale D, Glynn P (March 2003). "Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells". The Journal of Biological Chemistry. 278 (10): 8820–8825. doi:10.1074/jbc.M210743200. PMID 12514188.
- ↑ Zaccheo O, Dinsdale D, Meacock PA, Glynn P (June 2004). "Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells". The Journal of Biological Chemistry. 279 (23): 24024–24033. doi:10.1074/jbc.M400830200. PMID 15044461.
- ↑ Glynn P, Holton JL, Nolan CC, Read DJ, Brown L, Hubbard A, et al. (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. PMID 9466418. S2CID 7075276.
- ↑ Moser M, Li Y, Vaupel K, Kretzschmar D, Kluge R, Glynn P, et al. (February 2004). "Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice". Molecular and Cellular Biology. 24 (4): 1667–1679. doi:10.1128/mcb.24.4.1667-1679.2004. PMC 344166. PMID 14749382.
- ↑ Gallazzini M, Ferraris JD, Kunin M, Morris RG, Burg MB (October 2006). "Neuropathy target esterase catalyzes osmoprotective renal synthesis of glycerophosphocholine in response to high NaCl". Proceedings of the National Academy of Sciences of the United States of America. 103 (41): 15260–15265. Bibcode:2006PNAS..10315260G. doi:10.1073/pnas.0607133103. PMC 1622810. PMID 17015841.
- ↑ Mühlig-Versen M, da Cruz AB, Tschäpe JA, Moser M, Büttner R, Athenstaedt K, et al. (March 2005). "Loss of Swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila". The Journal of Neuroscience. 25 (11): 2865–2873. doi:10.1523/JNEUROSCI.5097-04.2005. PMC 1182176. PMID 15772346.
- ↑ Read DJ, Li Y, Chao MV, Cavanagh JB, Glynn P (September 2009). "Neuropathy target esterase is required for adult vertebrate axon maintenance". The Journal of Neuroscience. 29 (37): 11594–11600. doi:10.1523/JNEUROSCI.3007-09.2009. PMC 3849655. PMID 19759306.
- ↑ Gallazzini M, Burg MB (August 2009). "What's new about osmotic regulation of glycerophosphocholine". Physiology. 24 (4). Bethesda, Md.: 245–249. doi:10.1152/physiol.00009.2009. PMC 2943332. PMID 19675355.
- ↑ Rainier S, Bui M, Mark E, Thomas D, Tokarz D, Ming L, et al. (March 2008). "Neuropathy target esterase gene mutations cause motor neuron disease". American Journal of Human Genetics. 82 (3): 780–785. doi:10.1016/j.ajhg.2007.12.018. PMC 2427280. PMID 18313024.
- ↑ Rainier S, Albers JW, Dyck PJ, Eldevik OP, Wilcock S, Richardson RJ, et al. (January 2011). "Motor neuron disease due to neuropathy target esterase gene mutation: clinical features of the index families". Muscle & Nerve. 43 (1): 19–25. doi:10.1002/mus.21777. hdl:2027.42/78477. PMID 21171093. S2CID 1621142.
- ↑ Lotti M, Moretto A (2005). "Organophosphate-induced delayed polyneuropathy". Toxicological Reviews. 24 (1): 37–49. doi:10.2165/00139709-200524010-00003. PMID 16042503. S2CID 29313644.
- ↑ Cavanagh JB (August 1954). "The toxic effects of triortho-cresyl phosphate on the nervous system; an experimental study in hens". Journal of Neurology, Neurosurgery, and Psychiatry. 17 (3): 163–172. doi:10.1136/jnnp.17.3.163. PMC 503178. PMID 13192490.
- ↑ CASIDA JE, ETO M, BARON RL (September 1961). "Biological activity of a trio-cresyl phosphate metabolite". Nature. 191 (4796): 1396–1397. Bibcode:1961Natur.191.1396C. doi:10.1038/1911396a0. PMID 13877086. S2CID 4195141.
- ↑ Johnson MK (October 1969). "The delayed neurotoxic effect of some organophosphorus compounds. Identification of the phosphorylation site as an esterase". The Biochemical Journal. 114 (4): 711–717. doi:10.1042/bj1140711. PMC 1184957. PMID 4310054.
- ↑ Glynn P, Read DJ, Guo R, Wylie S, Johnson MK (July 1994). "Synthesis and characterization of a biotinylated organophosphorus ester for detection and affinity purification of a brain serine esterase: neuropathy target esterase". The Biochemical Journal. 301 ( Pt 2) (2): 551–556. doi:10.1042/bj3010551. PMC 1137116. PMID 8043002.
- ↑ 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". Toxicology and Applied Pharmacology. 245 (1): 108–115. Bibcode:2010ToxAP.245..108R. doi:10.1016/j.taap.2010.02.010. PMID 20188121.
Further reading
[edit]- Glynn P (May 2000). "Neural development and neurodegeneration: two faces of neuropathy target esterase". Progress in Neurobiology. 61 (1): 61–74. doi:10.1016/S0301-0082(99)00043-X. PMID 10759065. S2CID 20322620.
- Maroni M, Bleecker ML (1986). "Neuropathy target esterase in human lymphocytes and platelets". Journal of Applied Toxicology. 6 (1): 1–7. doi:10.1002/jat.2550060102. PMID 3958422. S2CID 21763818.
- Bertoncin D, Russolo A, Caroldi S, Lotti M (1985). "Neuropathy target esterase in human lymphocytes". Archives of Environmental Health. 40 (3): 139–144. doi:10.1080/00039896.1985.10545905. PMID 4026382.
- Gurba PE, Richardson RJ (1983). "Partial characterization of neurotoxic esterase of human placenta". Toxicology Letters. 15 (1): 13–17. Bibcode:1983ToxL...15...13G. doi:10.1016/0378-4274(83)90162-5. hdl:2027.42/25337. PMID 6836585.
- van Tienhoven M, Atkins J, Li Y, Glynn P (2002). "Human neuropathy target esterase catalyzes hydrolysis of membrane lipids". The Journal of Biological Chemistry. 277 (23): 20942–20948. doi:10.1074/jbc.M200330200. PMID 11927584.
- Winrow CJ, Hemming ML, Allen DM, Quistad GB, Casida JE, Barlow C (April 2003). "Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity". Nature Genetics. 33 (4): 477–485. Bibcode:2003NaGen..33..477W. doi:10.1038/ng1131. PMID 12640454.
- Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, et al. (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–12135. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
- Chang PA, Wu YJ, Chen R, Li M, Li W, Qin QL (April 2005). "Inhibition of neuropathy target esterase expressing by antisense RNA does not affect neural differentiation in human neuroblastoma (SK-N-SH) cell line". Molecular and Cellular Biochemistry. 272 (1–2): 47–54. doi:10.1007/s11010-005-6753-2. PMID 16010971. S2CID 20498617.
- Chang PA, Chen R, Wu YJ (2006). "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 Research. Molecular Brain Research. 141 (1): 30–38. doi:10.1016/j.molbrainres.2005.07.012. PMID 16122834. S2CID 22182434.
- Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
- Chang PA, Liu C, Chen R, Wu YJ (October 2006). "Effect of over-expression of neuropathy target esterase on mammalian cell proliferation". Cell Proliferation. 39 (5): 429–440. doi:10.1111/j.1365-2184.2006.00399.x. PMC 6496609. PMID 16987144.
- Chen R, Chang PA, Long DX, Yang L, Wu YJ (August 2007). "Down-regulation of neuropathy target esterase by protein kinase C activation with PMA stimulation". Molecular and Cellular Biochemistry. 302 (1–2): 179–185. doi:10.1007/s11010-007-9439-0. PMID 17385009. S2CID 1235494.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.