Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Maren Heimerl
 -- 1768 2022-09-01 09:31:49 |
2 update references and layout
Rita Xu
Meta information modification 1768 2022-09-01 10:35:35 | |
3 update description
Rita Xu
+ 19 word(s) 1787 2022-09-05 09:52:58 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Heimerl, M.;  Gausepohl, T.;  Mueller, J.H.;  Ricke-Hoch, M. Neuraminidases. Encyclopedia. Available online: https://encyclopedia.pub/entry/26777 (accessed on 27 July 2024).
Heimerl M,  Gausepohl T,  Mueller JH,  Ricke-Hoch M. Neuraminidases. Encyclopedia. Available at: https://encyclopedia.pub/entry/26777. Accessed July 27, 2024.
Heimerl, Maren, Thomas Gausepohl, Julia H. Mueller, Melanie Ricke-Hoch. "Neuraminidases" Encyclopedia, https://encyclopedia.pub/entry/26777 (accessed July 27, 2024).
Heimerl, M.,  Gausepohl, T.,  Mueller, J.H., & Ricke-Hoch, M. (2022, September 01). Neuraminidases. In Encyclopedia. https://encyclopedia.pub/entry/26777
Heimerl, Maren, et al. "Neuraminidases." Encyclopedia. Web. 01 September, 2022.
Neuraminidases
Edit
This entry is adapted from the peer-reviewed paper 10.3390/biology11081229

Neuraminidases (NEUs) are able to cleave off sugars termed sialic acids, which are terminally attached to glycolipids and -proteins. Glycoproteins and glycolipids on the cell surfaces of vertebrates and higher invertebrates contain α-keto acid sugars called sialic acids, terminally attached to their glycan structures. The actual level of sialylation, regulated through enzymatic removal of the latter ones by NEU enzymes, highly affects protein-protein, cell-matrix and cell-cell interactions. Thus, their regulatory features affect a large number of different cell types, including those of the immune system.

neuraminidase sialidase sialic acid sialylation desialylation glycosylation

1. Introduction

Vertebrate cell surfaces contain a complex array of sugar chains that are bound to lipids and proteins. Sialic acids are a diverse class of α-keto acid sugars characterized by a 9-C-backbone, widely found in animal tissues of all vertebrates [1][2]. They are essential components, positioned at the end of the sugar chains of many glycoproteins, glycolipids and gangliosides at the cell surface or at soluble proteins. Their ubiquitous distribution in glycoconjugates of various origins indicates that a variety of biological functions are associated with them [2]. Sialic acids play important roles in many physiological and pathological processes, e.g., cellular communication, cell assembly and development, mediation of viral and bacterial infections. In particular, they play a crucial role in the development of cardiovascular diseases, as they serve as ligands for leukocytes in the endothelium and are therefore involved in inflammation, atherosclerosis and reperfusion injuries [3][4][5]. NEUs are enzymes able to remove sialic acids, a process which is called desialylation, thus regulating the function of numerous different molecules [6][7].
The endothelial surface layer (ESL) is an important part of the vascular barrier. Coating the intimal surface in blood vessels, thereby creating a barrier separating endothelial cells, blood and neighbouring cells from each other, the ESL plays an important role in various immune reactions, including cardiovascular ones. As one component of the ESL, endothelial cells synthesize the polysaccharide-rich glycocalyx, which surrounds all eukaryotic cells. Consisting of negatively charged sialic acids (monosaccharides), which are in turn bound to proteoglycans, glycolipids and endothelial cells, the glycocalyx converts mechanical into biomechanical signals, thus greatly affecting inter- and intracellular communication and vascular homeostasis. This barrier is also of importance in matters of material and substrate exchange, thereby affecting inflammatory processes as well as vascular permeability, coagulation, blood flow and the complement system [8][9][10][11][12][13]. Individual components of the glycocalyx e.g., heparan sulphate proteoglycans, sialic acids and hyaluronic acid glycosaminoglycans are able to respond immediately to sensed shear stress, which is induced by the blood stream and affects the vessel’s wall, by the physiological production of nitric oxide (NO). NO, known for its vasodilatory effect, consequently modulates the vascular tone [13][14].

2. Mammalian Neuraminidases

The polysaccharide-rich glycocalyx can be altered in terms of sialylation by enzymes which are able to recognize sialic acid glycosidic bonds and thus enzymatically remove sialic acids. In mammals, four endogenous NEU enzymes, belonging to the glycoside hydrolase family and also known as sialidases, have been identified to date, namely NEU1, NEU2, NEU3 and NEU4. The catalysed removal of these negatively charged 9-C-backbone sugars, which are terminally attached to glycolipids and glycoproteins on the cell surface, highly affects the cells’ biophysical properties concerning protein-protein, cell-matrix and cell-cell interactions [1][6][15][16][17][18]. Most of the existing literature deals with desialylation by NEUs on the cell surface. However, due to localisation differences of the four NEU enzymes (Table 1), intracellular desialylation also takes place [19][20][21]. All four enzymes are encoded by different genes, own different enzymatic properties and prefer slightly different substrates. In addition, they can be distinguished by their different intracellular localisation [22].
Table 1. Overview of the four different mammalian NEUs and their isoform-specific properties.
Properties of the Four Mammalian NEU Enzymes  
  NEU1 NEU2 NEU3 NEU4
Human Gene Location chromosome 6p21.3 [23] chromosome 2q37 [24] chromosome 11q13.5 [24] chromosome 2q37.3 [24]
Murine Gene Location chromosome 17 [25] chromosome 1 [26] chromosome 7 [24] chromosome 10 [24]
Subcellular localisation Lysosomal, translocation towards the plasma membrane upon different stimuli [7][27][28] Cytosolic [24] Associated with the plasma membrane [29] Murine NEU4a and b, human NEU4S: ER membranes; human NEU4L: mitochondria, lysosomes [30][31]
Expression pattern kidneys, skeletal muscle, lung, placenta, brain, pancreas, inflammatory cells and cardiomyocytes [7][27][32][33] Muscle-specific isoform [7][34] Adrenal glands, heart, thymus, skeletal muscle and testis [7] Brain, heart, placenta, liver and skeletal muscle [31]
Substrate preferences Oligosaccharides with an α2,3 linkage [24] Oligosaccharides, gangliosides, glycoproteins [24][26][35] Gangliosides, most preferable with an α2,3 and α2,6 linkage [24] Oligosaccharides, gangliosides, glycoproteins [24]
Physiological functions Regulates exocytosis, modulator of inflammatory resposnse [27][36][37] Myoblast and neuronal cell differentiation [38][39][40] Neuronal cell differentitation, focal adhesion, cell invasion, cell survival, proliferation [41][42][43] Neural differentiation, mitochondrial neuronal apoptosis [44][45]

3. Functions and Implications of Neuraminidases

NEU1, initially described as a lysosomal protein playing a role in the catabolism of glycosylated proteins [7], is required to form a multienzyme complex with β-Galactosidase (β-GAL) and protective-protein/cathepsin (PPC) A in order to be catalytically active and stable. NEU1 can also homodimerize via the binding site which is usually utilized for binding to PPCA, however, once PPCA is available, the affinity of NEU1 to bind to it instead of binding to another NEU1 is stronger [46]. Further, this conjunction not only protects NEU1 from lysosomal degradation but is required for its transport towards the plasma membrane upon e.g., inflammatory cell activation or differentiation but also for its activation [27][47][48][49]. The gene coding for human NEU1 is located on chromosome 6p21.3 while the single gene for murine NEU1 is located on chromosome 17. Both protein products are 83% identical [23][25][50][51][52]. A reduction in NEU1 usually leads to severe diseases such as sialidosis [53] whereas increased levels stimulate inflammation and phagocytosis [32][54]. Further, NEU1 is a negative regulator of exocytosis [36][37].
There is only little known about the soluble protein NEU2 which is located in the cytosol and able to hydrolyse different glycoproteins, oligosaccharides and gangliosides [24][35]. The gene coding for human NEU2 is located on chromosome 2q37 [24] while its murine counterpart is located on chromosome 1 [26]. The exact role of NEU2 does not seem to be discovered yet. One reason might be lacking evidence which clearly demonstrates glycosidically bound sialic acids in the cytosol or on the inside of the plasma membrane [55], albeit, one study reports complex-type free sialylated N-glycans in the cytosol that were in turn degraded, likely due to the interaction of NEU2 and the cytosolic β-glycosidase (GBA) 3. NEU2 was stabilised by the latter one and both seem to be involved in a non-lysosomal catabolic degradation process [56]. In the physiological context, NEU2 seems to play a role in myoblast differentiation as an increased expression was observed during the differentiation of murine myoblasts. In this regard, experiments using NEU2 overexpressing clones which spontaneously underwent myoblast differentiation, showed that an upregulation of NEU2 per se sufficiently induces differentiation of myoblasts [38][39]. In addition to its role in myoblast differentiation, NEU2 also seems to be involved in the differentiation of neuronal cells derived from a tumour located in the adrenal medulla [40].
NEU3, per se associated with the plasma membrane, has additionally been reported to be translocated towards the plasma membrane in response to different stimuli, e.g., activation and differentiation of immune cells [29][57][58]. The gene coding for human NEU3 is located on chromosome 11q13.5 while its murine counterpart is located on chromosome 7 [24]. Like NEU2, NEU3 is also assigned a role in neuronal differentiation. However, for NEU3, a decreased expression and activity was shown to negatively interfere with cell proliferation while on the other hand promoting neurite extension, thereby inducing a shift towards cells with a differentiated phenotype [41]. In addition, NEU3 was shown to affect cell invasion and focal adhesion of glioblastoma cells, the former one though the regulation of calcium-dependent calpain [42]. Besides, the activation of the enzyme was shown to protect cultured skeletal muscle cells from hypoxia-induced apoptosis through the induction of the EGF receptor signalling pathway and thus, hypoxia inducible factor (HIF) 1α [43].
The gene encoding for human NEU4 is located on chromosome 2q37.3 and its murine counterpart on chromosome 10 [24]. The gene encodes for two different isoforms which holds true for both organisms. These isoforms are NEU4a and b in mice and NEU4L and S in humans, they differ in their first 12 N-terminal amino acids. Murine NEU4a and b have been reported to localize to endoplasmic reticulum (ER) membranes which are calnexin positive. NEU4L and S differ in their subcellular localization with NEU4L being present in mitochondria and lysosomes and NEU4S being present in membranes of the ER. The isoforms differ not only with regard to their localization but also in terms of their sialidase activity with NEU4b displaying a higher activity compared with the shorter isoform NEU4a [24][30][31][58][59]. Under certain conditions, a translocation of NEU4 towards the surface of cells has also been observed, however, the mechanisms behind that movement are not yet understood [24]. It has been proposed that NEU4 is, in connection with NEU3, involved in neural differentiation [60]. NEU4L, expressed in mitochondria as mentioned earlier, seems to be involved in the mitochondrial apoptotic pathway in neuronal cells [44][61].
Human NEU1 bears only a minor resemblance of approximately 19–24% to the other three NEUs with regard to its DNA sequence whereas these exhibit a similarity of 34–40% to each other. In line with this, the binding pocket of NEU1 is also distinct from the one of the other NEU enzymes [24]. However, for an optimal activity, all four human NEU enzymes need an ideal pH environment which is defined between acidic 3.5 and 5.5 [18].
In summary, the four endogenous mammalian NEU enzymes, each encoded by a different gene, exhibit different enzymatic characteristics which subsequently result in partly different substrate specificities as well as different intracellular localization.

4. Occurrence and Substrate Specificity of Neuraminidases

All 4 NEUs differ with regard to their expression pattern. NEU1 is ubiquitously expressed and most abundant in kidneys, skeletal muscle, lung, placenta, brain, pancreas, inflammatory cells and cardiomyocytes whereas NEU2 depicts a muscle-specific isoform. NEU3 on the other hand is mostly expressed in the adrenal glands, heart, thymus, skeletal muscle and testis, and NEU4 in the brain, heart, placenta, liver and skeletal muscle [7][27][32][33][52][62]. In mammals, among all 4 NEU enzymes, NEU1 is the most abundant one [15].
The enzymatic removal of sialic acids represents a regulatory function of NEU enzymes through which they highly affect intra- and intercellular communication. The entirety of sialic acid types and underlying connections is versatile due to the fact that these α-keto acids occur in different forms and with different underlying linkages [6][63][64]. Due to these varieties, it is no surprise that the NEU enzymes differ from each other in terms of substrate preferences. Even though NEU1, 2 and 4 share oligosaccharides as substrates, NEU1 prefers those joined with an α2,3 linkage. Sialic acid containing glycosphingolipids, so called gangliosides, belong to the substrate group of all NEU enzymes except for NEU1. Eventually, gangliosides seem to be the only substrates of NEU3, most preferable those with an α2,3 and α2,6 binding. NEU2 and NEU4 share the feature of a broad substrate specificity including, next to already mentioned oligosaccharides, glycoproteins and gangliosides [24][35][58].

References

  1. Varki, A.; Gagneux, P. Multifarious roles of sialic acids in immunity. Ann. N. Y. Acad. Sci. 2012, 1253, 16–36.
  2. Varki, A. Sialic acids in human health and disease. Trends Mol. Med. 2008, 14, 351–360.
  3. Zhou, X.; Yang, G.; Guan, F. Biological Functions and Analytical Strategies of Sialic Acids in Tumor. Cells 2020, 9, 273.
  4. Poznyak, A.V.; Zhang, D.; Grechko, A.V.; Wu, W.K.; Orekhov, A.N. The role of sialic acids in the initiation of atherosclerosis. Minerva Cardioangiol. 2020, 68, 359–364.
  5. Rosenstock, P.; Kaufmann, T. Sialic Acids and Their Influence on Human NK Cell Function. Cells 2021, 10, 263.
  6. Lubbers, J.; Rodriguez, E.; van Kooyk, Y. Modulation of Immune Tolerance via Siglec-Sialic Acid Interactions. Front. Immunol. 2018, 9, 2807.
  7. Pshezhetsky, A.V.; Ashmarina, L.I. Desialylation of surface receptors as a new dimension in cell signaling. Biochemistry 2013, 78, 736–745.
  8. Masola, V.; Zaza, G.; Arduini, A.; Onisto, M.; Gambaro, G. Endothelial Glycocalyx as a Regulator of Fibrotic Processes. Int. J. Mol. Sci. 2021, 22, 2996.
  9. Lepedda, A.J.; Nieddu, G.; Piperigkou, Z.; Kyriakopoulou, K.; Karamanos, N.; Formato, M. Circulating Heparan Sulfate Proteoglycans as Biomarkers in Health and Disease. Semin Thromb. Hemost 2021, 47, 295–307.
  10. Tarbell, J.M.; Cancel, L.M. The glycocalyx and its significance in human medicine. J. Intern. Med. 2016, 280, 97–113.
  11. Pries, A.R.; Secomb, T.W.; Gaehtgens, P. The endothelial surface layer. Pflugers Arch. 2000, 440, 653–666.
  12. Sieve, I.; Munster-Kuhnel, A.K.; Hilfiker-Kleiner, D. Regulation and function of endothelial glycocalyx layer in vascular diseases. Vasc. Pharmacol. 2018, 100, 26–33.
  13. Potje, S.R.; Paula, T.D.; Paulo, M.; Bendhack, L.M. The Role of Glycocalyx and Caveolae in Vascular Homeostasis and Diseases. Front. Physiol. 2020, 11, 620840.
  14. Urschel, K.; Tauchi, M.; Achenbach, S.; Dietel, B. Investigation of Wall Shear Stress in Cardiovascular Research and in Clinical Practice-From Bench to Bedside. Int. J. Mol. Sci. 2021, 22, 5635.
  15. Zhang, J.Y.; Chen, Q.Q.; Li, J.; Zhang, L.; Qi, L.W. Neuraminidase 1 and its Inhibitors from Chinese Herbal Medicines: An Emerging Role for Cardiovascular Diseases. Am. J. Chin. Med. 2021, 49, 843–862.
  16. Rota, P.; La Rocca, P.; Allevi, P.; Pappone, C.; Anastasia, L. Intramolecular Lactones of Sialic Acids. Int. J. Mol. Sci. 2020, 21, 8098.
  17. Schauer, R. Sialic acids as regulators of molecular and cellular interactions. Curr. Opin. Struct. Biol. 2009, 19, 507–514.
  18. Bourguet, E.; Figurska, S.; Fra Czek, M.M. Human Neuraminidases: Structures and Stereoselective Inhibitors. J. Med. Chem. 2022, 65, 3002–3025.
  19. Kim, Y.J.; Varki, A. Perspectives on the significance of altered glycosylation of glycoproteins in cancer. Glycoconj. J. 1997, 14, 569–576.
  20. Dennis, J.W.; Granovsky, M.; Warren, C.E. Protein glycosylation in development and disease. Bioessays 1999, 21, 412–421.
  21. Krzeslak, A.; Gaj, Z.; Pomorski, L.; Lipinska, A. Sialylation of intracellular proteins of thyroid lesions. Oncol. Rep. 2007, 17, 1237–1242.
  22. Glanz, V.Y.; Myasoedova, V.A.; Grechko, A.V.; Orekhov, A.N. Sialidase activity in human pathologies. Eur. J. Pharmacol. 2019, 842, 345–350.
  23. Seyrantepe, V.; Poupetova, H.; Froissart, R.; Zabot, M.T.; Maire, I.; Pshezhetsky, A.V. Molecular pathology of NEU1 gene in sialidosis. Hum. Mutat. 2003, 22, 343–352.
  24. Miyagi, T.; Yamaguchi, K. Mammalian sialidases: Physiological and pathological roles in cellular functions. Glycobiology 2012, 22, 880–896.
  25. Womack, J.E.; Yan, D.L.; Potier, M. Gene for neuraminidase activity on mouse chromosome 17 near h-2: Pleiotropic effects on multiple hydrolases. Science 1981, 212, 63–65.
  26. Kijimoto-Ochiai, S.; Koda, T.; Suwama, T.; Matsukawa, H.; Fujii, M.; Tomobe, K.; Nishimura, M. Low expression of Neu2 sialidase in the thymus of SM/J mice-existence of neuraminidase positive cells “Neu-medullocyte” in the murine thymus. Glycoconj. J. 2008, 25, 787–796.
  27. Heimerl, M.; Sieve, I.; Ricke-Hoch, M.; Erschow, S.; Battmer, K.; Scherr, M.; Hilfiker-Kleiner, D. Neuraminidase-1 promotes heart failure after ischemia/reperfusion injury by affecting cardiomyocytes and invading monocytes/macrophages. Basic Res. Cardiol. 2020, 115, 62.
  28. Liang, F.; Seyrantepe, V.; Landry, K.; Ahmad, R.; Ahmad, A.; Stamatos, N.M.; Pshezhetsky, A.V. Monocyte differentiation up-regulates the expression of the lysosomal sialidase, Neu1, and triggers its targeting to the plasma membrane via major histocompatibility complex class II-positive compartments. J. Biol. Chem. 2006, 281, 27526–27538.
  29. Howlader, M.A.; Li, C.; Zou, C.; Chakraberty, R.; Ebesoh, N.; Cairo, C.W. Neuraminidase-3 Is a Negative Regulator of LFA-1 Adhesion. Front. Chem. 2019, 7, 791.
  30. Timur, Z.K.; Inci, O.K.; Demir, S.A.; Seyrantepe, V. Sialidase neu4 deficiency is associated with neuroinflammation in mice. Glycoconj. J. 2021, 38, 649–667.
  31. Monti, E.; Bassi, M.T.; Bresciani, R.; Civini, S.; Croci, G.L.; Papini, N.; Riboni, M.; Zanchetti, G.; Ballabio, A.; Preti, A.; et al. Molecular cloning and characterization of NEU4, the fourth member of the human sialidase gene family. Genomics 2004, 83, 445–453.
  32. Sieve, I.; Ricke-Hoch, M.; Kasten, M.; Battmer, K.; Stapel, B.; Falk, C.S.; Leisegang, M.S.; Haverich, A.; Scherr, M.; Hilfiker-Kleiner, D. A positive feedback loop between IL-1beta, LPS and NEU1 may promote atherosclerosis by enhancing a pro-inflammatory state in monocytes and macrophages. Vasc. Pharmacol. 2018, 103–105, 16–28.
  33. Chen, Q.Q.; Ma, G.; Liu, J.F.; Cai, Y.Y.; Zhang, J.Y.; Wei, T.T.; Pan, A.; Jiang, S.; Xiao, Y.; Xiao, P.; et al. Neuraminidase 1 is a driver of experimental cardiac hypertrophy. Eur. Heart J. 2021, 42, 3770–3782.
  34. Oh, M.; Ha, D.I.; Son, C.; Kang, J.G.; Hwang, H.; Moon, S.B.; Kim, M.; Nam, J.; Kim, J.S.; Song, S.Y.; et al. Defect in cytosolic Neu2 sialidase abrogates lipid metabolism and impairs muscle function in vivo. Sci. Rep. 2022, 12, 3216.
  35. Tringali, C.; Papini, N.; Fusi, P.; Croci, G.; Borsani, G.; Preti, A.; Tortora, P.; Tettamanti, G.; Venerando, B.; Monti, E. Properties of recombinant human cytosolic sialidase HsNEU2. The enzyme hydrolyzes monomerically dispersed GM1 ganglioside molecules. J. Biol. Chem. 2004, 279, 3169–3179.
  36. Chen, S.; Li, M.; Jiang, W.; Zheng, H.; Qi, L.W.; Jiang, S. The role of Neu1 in the protective effect of dipsacoside B on acetaminophen-induced liver injury. Ann. Transl. Med. 2020, 8, 823.
  37. Annunziata, I.; Patterson, A.; Helton, D.; Hu, H.; Moshiach, S.; Gomero, E.; Nixon, R.; d’Azzo, A. Lysosomal NEU1 deficiency affects amyloid precursor protein levels and amyloid-beta secretion via deregulated lysosomal exocytosis. Nat. Commun. 2013, 4, 2734.
  38. Fanzani, A.; Giuliani, R.; Colombo, F.; Zizioli, D.; Presta, M.; Preti, A.; Marchesini, S. Overexpression of cytosolic sialidase Neu2 induces myoblast differentiation in C2C12 cells. FEBS Lett. 2003, 547, 183–188.
  39. Fanzani, A.; Colombo, F.; Giuliani, R.; Preti, A.; Marchesini, S. Insulin-like growth factor 1 signaling regulates cytosolic sialidase Neu2 expression during myoblast differentiation and hypertrophy. FEBS J. 2006, 273, 3709–3721.
  40. Fanzani, A.; Colombo, F.; Giuliani, R.; Preti, A.; Marchesini, S. Cytosolic sialidase Neu2 upregulation during PC12 cells differentiation. FEBS Lett. 2004, 566, 178–182.
  41. Valaperta, R.; Valsecchi, M.; Rocchetta, F.; Aureli, M.; Prioni, S.; Prinetti, A.; Chigorno, V.; Sonnino, S. Induction of axonal differentiation by silencing plasma membrane-associated sialidase Neu3 in neuroblastoma cells. J. Neurochem. 2007, 100, 708–719.
  42. Takahashi, K.; Proshin, S.; Yamaguchi, K.; Yamashita, Y.; Katakura, R.; Yamamoto, K.; Shima, H.; Hosono, M.; Miyagi, T. Sialidase NEU3 defines invasive potential of human glioblastoma cells by regulating calpain-mediated proteolysis of focal adhesion proteins. Biochim. Biophys. Acta Gen. Subj. 2017, 1861, 2778–2788.
  43. Scaringi, R.; Piccoli, M.; Papini, N.; Cirillo, F.; Conforti, E.; Bergante, S.; Tringali, C.; Garatti, A.; Gelfi, C.; Venerando, B.; et al. NEU3 sialidase is activated under hypoxia and protects skeletal muscle cells from apoptosis through the activation of the epidermal growth factor receptor signaling pathway and the hypoxia-inducible factor (HIF)-1alpha. J. Biol. Chem. 2013, 288, 3153–3162.
  44. Yamaguchi, K.; Hata, K.; Koseki, K.; Shiozaki, K.; Akita, H.; Wada, T.; Moriya, S.; Miyagi, T. Evidence for mitochondrial localization of a novel human sialidase (NEU4). Biochem. J. 2005, 390, 85–93.
  45. Shiozaki, K.; Koseki, K.; Yamaguchi, K.; Shiozaki, M.; Narimatsu, H.; Miyagi, T. Developmental change of sialidase neu4 expression in murine brain and its involvement in the regulation of neuronal cell differentiation. J. Biol. Chem. 2009, 284, 21157–21164.
  46. Bonten, E.J.; Campos, Y.; Zaitsev, V.; Nourse, A.; Waddell, B.; Lewis, W.; Taylor, G.; d’Azzo, A. Heterodimerization of the sialidase NEU1 with the chaperone protective protein/cathepsin A prevents its premature oligomerization. J. Biol. Chem. 2009, 284, 28430–28441.
  47. Luu, A.R.; Wong, C.; Agrawal, V.; Wise, N.; Handyside, B.; Lo, M.J.; Pacheco, G.; Felix, J.B.; Giaramita, A.; d’Azzo, A.; et al. Intermittent enzyme replacement therapy with recombinant human beta-galactosidase prevents neuraminidase 1 deficiency. J. Biol. Chem. 2020, 295, 13556–13569.
  48. Van Diggelen, O.P.; Schram, A.W.; Sinnott, M.L.; Smith, P.J.; Robinson, D.; Galjaard, H. Turnover of beta-galactosidase in fibroblasts from patients with genetically different types of beta-galactosidase deficiency. Biochem. J. 1981, 200, 143–151.
  49. van der Spoel, A.; Bonten, E.; d’Azzo, A. Transport of human lysosomal neuraminidase to mature lysosomes requires protective protein/cathepsin A. EMBO J. 1998, 17, 1588–1597.
  50. Carrillo, M.B.; Milner, C.M.; Ball, S.T.; Snoek, M.; Campbell, R.D. Cloning and characterization of a sialidase from the murine histocompatibility-2 complex: Low levels of mRNA and a single amino acid mutation are responsible for reduced sialidase activity in mice carrying the Neu1a allele. Glycobiology 1997, 7, 975–986.
  51. Milner, C.M.; Smith, S.V.; Carrillo, M.B.; Taylor, G.L.; Hollinshead, M.; Campbell, R.D. Identification of a sialidase encoded in the human major histocompatibility complex. J. Biol. Chem. 1997, 272, 4549–4558.
  52. 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. 1996, 10, 3156–3169.
  53. Ahn, J.H.; Kim, A.R.; Lee, C.; Kim, N.K.D.; Kim, N.S.; Park, W.Y.; Kim, M.; Youn, J.; Cho, J.W.; Kim, J.S. Type 1 Sialidosis Patient With a Novel Deletion Mutation in the NEU1 Gene: Case Report and Literature Review. Cerebellum 2019, 18, 659–664.
  54. Khan, A.; Das, S.; Sergi, C. Therapeutic Potential of Neu1 in Alzheimer’s Disease Via the Immune System. Am. J. Alzheimers Dis. Other Demen. 2021, 36, 1533317521996147.
  55. Varki, A.; Schauer, R. Sialic Acids. In Essentials of Glycobiology, 2nd ed.; Varki, A., Cummings, R.D., Esko, J.D., Freeze, H.H., Stanley, P., Bertozzi, C.R., Hart, G.W., Etzler, M.E., Eds.; Cold Spring Harbor (NY): New York, NY, USA, 2009.
  56. Wang, L.; Seino, J.; Tomotake, H.; Funakoshi, Y.; Hirayama, H.; Suzuki, T. Co-Expression of NEU2 and GBA3 Causes a Drastic Reduction in Cytosolic Sialyl Free N-glycans in Human MKN45 Stomach Cancer Cells-Evidence for the Physical Interaction of NEU2 and GBA3. Biomolecules 2015, 5, 1499–1514.
  57. Breiden, B.; Sandhoff, K. Ganglioside Metabolism and Its Inherited Diseases. Methods Mol. Biol. 2018, 1804, 97–141.
  58. Smutova, V.; Albohy, A.; Pan, X.; Korchagina, E.; Miyagi, T.; Bovin, N.; Cairo, C.W.; Pshezhetsky, A.V. Structural basis for substrate specificity of mammalian neuraminidases. PLoS ONE 2014, 9, e106320.
  59. Bigi, A.; Morosi, L.; Pozzi, C.; Forcella, M.; Tettamanti, G.; Venerando, B.; Monti, E.; Fusi, P. Human sialidase NEU4 long and short are extrinsic proteins bound to outer mitochondrial membrane and the endoplasmic reticulum, respectively. Glycobiology 2010, 20, 148–157.
  60. Bigi, A.; Tringali, C.; Forcella, M.; Mozzi, A.; Venerando, B.; Monti, E.; Fusi, P. A proline-rich loop mediates specific functions of human sialidase NEU4 in SK-N-BE neuronal differentiation. Glycobiology 2013, 23, 1499–1509.
  61. De Maria, R.; Lenti, L.; Malisan, F.; d’Agostino, F.; Tomassini, B.; Zeuner, A.; Rippo, M.R.; Testi, R. Requirement for GD3 ganglioside in CD95- and ceramide-induced apoptosis. Science 1997, 277, 1652–1655.
  62. Comelli, E.M.; Amado, M.; Lustig, S.R.; Paulson, J.C. Identification and expression of Neu4, a novel murine sialidase. Gene 2003, 321, 155–161.
  63. Schauer, R.; Kamerling, J.P. Exploration of the Sialic Acid World. Adv. Carbohydr. Chem. Biochem. 2018, 75, 1–213.
  64. Cohen, M.; Varki, A. The sialome-far more than the sum of its parts. OMICS 2010, 14, 455–464.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Maren Heimerl
,
Thomas Gausepohl
,
Julia H. Mueller
,
Melanie Ricke-Hoch
View Times: 404
Revisions: 3 times (View History)
Update Date: 05 Sep 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback