Sialidase-1 Explained

Sialidase-1, is a mammalian lysosomal neuraminidase enzyme which in humans is encoded by the NEU1 gene.^{[1] [2]}

Function

The protein SIALIDASE-1 encoded by the NEU-1 gene encodes the lysosomal enzyme SIALIDASE-1, which cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids. In the lysosome, this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter also referred to as 'protective protein'). Mutations in this gene can lead to sialidosis.^[1]

Clinical significance

Mutations in NEU1 leads to sialidosis, a rare lysosomal storage disease.^[3] Sialidase has also been shown to enhance recovery from spinal cord contusion injury when injected in rats.^[4]

Interactions

NEU1 has been shown to interact with Cathepsin A.^[5]

References

Further reading

• Okamura-Oho Y, Zhang S, Callahan JW . The biochemistry and clinical features of galactosialidosis . Biochim. Biophys. Acta . 1225 . 3 . 244–54 . 1994 . 8312369 . 10.1016/0925-4439(94)90002-7 .
• Seyrantepe V, Poupetova H, Froissart R, Zabot MT, Maire I, Pshezhetsky AV . Molecular pathology of NEU1 gene in sialidosis . Hum. Mutat. . 22 . 5 . 343–52 . 2004 . 14517945 . 10.1002/humu.10268 . 22333886 .
• Verheijen FW, Palmeri S, Galjaard H . Purification and partial characterization of lysosomal neuraminidase from human placenta . Eur. J. Biochem. . 162 . 1 . 63–7 . 1987 . 3102233 . 10.1111/j.1432-1033.1987.tb10542.x .
• Verheijen FW, Palmeri S, Hoogeveen AT, Galjaard H . Human placental neuraminidase. Activation, stabilization and association with beta-galactosidase and its protective protein . Eur. J. Biochem. . 149 . 2 . 315–21 . 1985 . 3922758 . 10.1111/j.1432-1033.1985.tb08928.x .
• Hu H, Shioda T, Moriya C, Xin X, Hasan MK, Miyake K, Shimada T, Nagai Y . Infectivities of human and other primate lentiviruses are activated by desialylation of the virion surface . J. Virol. . 70 . 11 . 7462–70 . 1996 . 8892864 . 190813 . 10.1128/JVI.70.11.7462-7470.1996.
• Pshezhetsky AV, Potier M . Association of N-acetylgalactosamine-6-sulfate sulfatase with the multienzyme lysosomal complex of beta-galactosidase, cathepsin A, and neuraminidase. Possible implication for intralysosomal catabolism of keratan sulfate . J. Biol. Chem. . 271 . 45 . 28359–65 . 1996 . 8910459 . 10.1074/jbc.271.45.28359 . free .
• Bonten E, van der Spoel A, Fornerod M, Grosveld G, d'Azzo A . Characterization of human lysosomal neuraminidase defines the molecular basis of the metabolic storage disorder sialidosis . Genes Dev. . 10 . 24 . 3156–69 . 1997 . 8985184 . 10.1101/gad.10.24.3156 . free . * Milner CM, Smith SV, Carrillo MB, Taylor GL, Hollinshead M, Campbell RD . Identification of a sialidase encoded in the human major histocompatibility complex . J. Biol. Chem. . 272 . 7 . 4549–58 . 1997 . 9020182 . 10.1074/jbc.272.7.4549 . free .
• Pshezhetsky AV, Richard C, Michaud L, Igdoura S, Wang S, Elsliger MA, Qu J, Leclerc D, Gravel R, Dallaire L, Potier M . Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis . Nat. Genet. . 15 . 3 . 316–20 . 1997 . 9054950 . 10.1038/ng0397-316 . 31588761 .
• Vinogradova MV, Michaud L, Mezentsev AV, Lukong KE, El-Alfy M, Morales CR, Potier M, Pshezhetsky AV . Molecular mechanism of lysosomal sialidase deficiency in galactosialidosis involves its rapid degradation . Biochem. J. . 330 (Pt 2) . Pt 2 . 641–50 . 1998 . 9480870 . 1219185 . 10.1042/bj3300641.
• van der Spoel A, Bonten E, d'Azzo A . Transport of human lysosomal neuraminidase to mature lysosomes requires protective protein/cathepsin A . EMBO J. . 17 . 6 . 1588–97 . 1998 . 9501080 . 1170506 . 10.1093/emboj/17.6.1588 .
• Lukong KE, Elsliger MA, Chang Y, Richard C, Thomas G, Carey W, Tylki-Szymanska A, Czartoryska B, Buchholz T, Criado GR, Palmeri S, Pshezhetsky AV . Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex . Hum. Mol. Genet. . 9 . 7 . 1075–85 . 2000 . 10767332 . 10.1093/hmg/9.7.1075 . free .
• Naganawa Y, Itoh K, Shimmoto M, Takiguchi K, Doi H, Nishizawa Y, Kobayashi T, Kamei S, Lukong KE, Pshezhetsky AV, Sakuraba H . Molecular and structural studies of Japanese patients with sialidosis type 1 . J. Hum. Genet. . 45 . 4 . 241–9 . 2000 . 10944856 . 10.1007/s100380070034 . free .
• Bonten EJ, Arts WF, Beck M, Covanis A, Donati MA, Parini R, Zammarchi E, d'Azzo A . Novel mutations in lysosomal neuraminidase identify functional domains and determine clinical severity in sialidosis . Hum. Mol. Genet. . 9 . 18 . 2715–25 . 2000 . 11063730 . 10.1093/hmg/9.18.2715 . free .
• Lukong KE, Landry K, Elsliger MA, Chang Y, Lefrancois S, Morales CR, Pshezhetsky AV . Mutations in sialidosis impair sialidase binding to the lysosomal multienzyme complex . J. Biol. Chem. . 276 . 20 . 17286–90 . 2001 . 11279074 . 10.1074/jbc.M100460200 . free .
• Penzel R, Uhl J, Kopitz J, Beck M, Otto HF, Cantz M . Splice donor site mutation in the lysosomal neuraminidase gene causing exon skipping and complete loss of enzyme activity in a sialidosis patient . FEBS Lett. . 501 . 2–3 . 135–8 . 2001 . 11470272 . 10.1016/S0014-5793(01)02645-X . 27689049 . free . 2001FEBSL.501..135P . * Lukong KE, Seyrantepe V, Landry K, Trudel S, Ahmad A, Gahl WA, Lefrancois S, Morales CR, Pshezhetsky AV . Intracellular distribution of lysosomal sialidase is controlled by the internalization signal in its cytoplasmic tail . J. Biol. Chem. . 276 . 49 . 46172–81 . 2002 . 11571282 . 10.1074/jbc.M104547200 . free .
• Sergi C, Penzel R, Uhl J, Zoubaa S, Dietrich H, Decker N, Rieger P, Kopitz J, Otto HF, Kiessling M, Cantz M . Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal alpha-N-acetyl-neuraminidase (sialidase) gene . Hum. Genet. . 109 . 4 . 421–8 . 2001 . 11702224 . 10.1007/s004390100592 . 24374154 .
• Itoh K, Naganawa Y, Matsuzawa F, Aikawa S, Doi H, Sasagasako N, Yamada T, Kira J, Kobayashi T, Pshezhetsky AV, Sakuraba H . Novel missense mutations in the human lysosomal sialidase gene in sialidosis patients and prediction of structural alterations of mutant enzymes . J. Hum. Genet. . 47 . 1 . 29–37 . 2002 . 11829139 . 10.1007/s10038-002-8652-7 . free .

Notes and References

1. Web site: Entrez Gene: NEU1 sialidase 1 (lysosomal sialidase).
2. Pshezhetsky AV, Richard C, Michaud L, Igdoura S, Wang S, Elsliger MA, Qu J, Leclerc D, Gravel R, Dallaire L, Potier M . Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis . Nat. Genet. . 15 . 3 . 316–20 . March 1997 . 9054950 . 10.1038/ng0397-316 . 31588761 .
3. Seyrantepe V, Poupetova H, Froissart R, Zabot MT, Maire I, Pshezhetsky AV . Molecular pathology of NEU1 gene in sialidosis . Hum. Mutat. . 22 . 5 . 343–52 . November 2003 . 14517945 . 10.1002/humu.10268 . 22333886 .
4. Mountney A, Zahner MR, Lorenzini I, Oudega M, Schramm LP, Schnaar RL . Sialidase enhances recovery from spinal cord contusion injury . PNAS . 107 . 25 . 11561–6 . June 2010 . 20534525 . 2895144 . 10.1073/pnas.1006683107 . 2010PNAS..10711561M . free .
5. van der Spoel A, Bonten E, d'Azzo A . Transport of human lysosomal neuraminidase to mature lysosomes requires protective protein/cathepsin A . EMBO J. . 17 . 6 . 1588–97 . Mar 1998 . 9501080 . 1170506 . 10.1093/emboj/17.6.1588 .