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Neuropathy target esterase

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(Redirected from PNPLA6)

PNPLA6
Identifiers
AliasesPNPLA6, BNHS, NTE, NTEMND, SPG39, iPLA2delta, sws, LNMS, OMCS, patatin like phospholipase domain containing 6
External IDsOMIM: 603197; MGI: 1354723; HomoloGene: 21333; GeneCards: PNPLA6; OMA:PNPLA6 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

10908

50767

Ensembl

ENSG00000032444

ENSMUSG00000004565

UniProt

Q8IY17

Q3TRM4

RefSeq (mRNA)

NM_006702
NM_001166111
NM_001166112
NM_001166113
NM_001166114

RefSeq (protein)

NP_001159583
NP_001159584
NP_001159585
NP_001159586
NP_006693

Location (UCSC)Chr 19: 7.53 – 7.56 MbChr 8: 3.57 – 3.59 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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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

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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.[8]

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.[19][20] Organophosphate-induced delayed neuropathy— a paralysing syndrome with distal degeneration of long axons— results from poisoning with neuropathic organophosphorus compounds that irreversibly inhibit NTE.[21][22][23][24][25][26]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000032444 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000004565 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Lush MJ, Li Y, Read DJ, Willis AC, Glynn P (Aug 1998). "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. doi:10.1042/bj3320001. PMC 1219444. PMID 9576844.
  6. ^ Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ (Aug 2006). "Characterization of the human patatin-like phospholipase family". J Lipid Res. 47 (9): 1940–9. doi:10.1194/jlr.M600185-JLR200. PMID 16799181.
  7. ^ Kienesberger PC, Oberer M, Lass A, Zechner R (Apr 2009). "Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions". J Lipid Res. 50 Suppl (Supplement): S63–8. doi:10.1194/jlr.R800082-JLR200. PMC 2674697. PMID 19029121.
  8. ^ a b c "Entrez Gene: PNPLA6 patatin-like phospholipase domain containing 6".
  9. ^ 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.
  10. ^ 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. PMID 16731034.
  11. ^ 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. PMID 12514188.
  12. ^ 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. PMID 15044461.
  13. ^ 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.
  14. ^ 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". Mol. Cell. Biol. 24 (4): 1667–79. doi:10.1128/mcb.24.4.1667-1679.2004. PMC 344166. PMID 14749382.
  15. ^ 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". Proc. Natl. Acad. Sci. U.S.A. 103 (41): 15260–5. Bibcode:2006PNAS..10315260G. doi:10.1073/pnas.0607133103. PMC 1622810. PMID 17015841.
  16. ^ 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". J. Neurosci. 25 (11): 2865–73. doi:10.1523/JNEUROSCI.5097-04.2005. PMC 1182176. PMID 15772346.
  17. ^ Read DJ, Li Y, Chao MV, Cavanagh JB, Glynn P (September 2009). "Neuropathy target esterase is required for adult vertebrate axon maintenance". J. Neurosci. 29 (37): 11594–600. doi:10.1523/JNEUROSCI.3007-09.2009. PMC 3849655. PMID 19759306.
  18. ^ Gallazzini M, Burg MB (2009). "What's New About Osmotic Regulation of Glycerophosphocholine". Physiology. 24 (4): 245–249. doi:10.1152/physiol.00009.2009. PMC 2943332. PMID 19675355.
  19. ^ 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". Am. J. Hum. Genet. 82 (3): 780–5. doi:10.1016/j.ajhg.2007.12.018. PMC 2427280. PMID 18313024.
  20. ^ 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.
  21. ^ Lotti M, Moretto A (2005). "Organophosphate-induced delayed polyneuropathy". Toxicol Rev. 24 (1): 37–49. doi:10.2165/00139709-200524010-00003. PMID 16042503. S2CID 29313644.
  22. ^ 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. PMC 503178. PMID 13192490.
  23. ^ CASIDA JE, ETO M, BARON RL (September 1961). "Biological activity of a trio-cresyl phosphate metabolite". Nature. 191 (4796): 1396–7. Bibcode:1961Natur.191.1396C. doi:10.1038/1911396a0. PMID 13877086. S2CID 4195141.
  24. ^ 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. PMC 1184957. PMID 4310054.
  25. ^ 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". Biochem. J. 301 ( Pt 2) (2): 551–6. doi:10.1042/bj3010551. PMC 1137116. PMID 8043002.
  26. ^ 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. PMID 20188121.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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