Disease relevance of Neu1

• Mice nullizygous at the Neu1 locus develop clinical abnormalities reminiscent of early-onset sialidosis in children, including severe nephropathy, progressive edema, splenomegaly, kyphosis and urinary excretion of sialylated oligosaccharides [1].
• In this study we tested the therapeutic efficacy of baculovirus (BV) expressed mouse neuraminidase (Neu1) in sialidosis mice [2].
• We found that minority subsets of such particles did produce plaques, provided they were activated by trypsin (analogous to other abortive systems producing virions with uncleaved HA), a step obviated for some WSN virions by indirect promotion of hemagglutinin cleavage by the neuraminidase of that strain [3].
• Induction of axonal differentiation by silencing plasma membrane-associated sialidase Neu3 in neuroblastoma cells [4].
• From the reassortment experiments between A/Aichi/4/92 and A/WSN/33 (WSN) (H1N1) viruses, two different phenotype viruses which contained the haemagglutinin (HA) gene from A/Aichi/4/92 virus and the neuraminidase (NA) gene from WSN virus were obtained [5].

Psychiatry related information on Neu1

• Neuraminidase treatment of proteoglycan-deficient cells restores permissiveness to GDVII virus, indicating that sialic acid hinders direct access of virus to the protein entry receptor [6].
• Adsorption experiments indicated that the PY206 Id was borne by antibodies specific for viral hemagglutinin (HA) and/or neuraminidase (NA) [7].

High impact information on Neu1

• Initial biochemical characterization of the target epitope reveals that it is a lipid present in chloroform/methanol extracts from perinatal retina and is sensitive to neuraminidase digestion [8].
• There is evidence that part of this recycling process involves the distal region of the Golgi complex, where terminal glycosylation occurs: when the plasma membrane transferrin receptor is desialylated by neuraminidase treatment, it acquires new sialic acid molecules after endocytosis and before cell-surface re-expression [9].
• This inducible event appears to be a coordinately regulated system dependent on trypsin- and neuraminidase-sensitive structures present on the epithelial cell surface [10].
• Sensitization required the inactivation of viral neuraminidase activity and could be inhibited by preventing fusion of viral and cellular membranes [11].
• Treatment of sections with sialidase eliminated the binding of lymphocytes to peripheral lymph node HEV, had no effect on binding to Peyer's patch HEV, and had an intermediate effect on mesenteric lymph node HEV [12].

Chemical compound and disease context of Neu1

• In essence, virion NA was isolated from detergent-disrupted virus by affinity chromatography on oxamic acid-agarose, treated with formalin and tested for its enzymatic activity and for its immunogenicity in Balb/c mice and New Zealand rabbits [13].
• A murine I-Ed-restricted T cell hybridoma recognizing the neuraminidase (NA) glycoprotein of influenza PR8 virus was stimulated strongly by infectious virus but failed to recognize antigen introduced on noninfectious virions [14].
• In L-929 cells abortively infected with fowl plague virus, matrix (M) protein synthesis is specifically inhibited, whereas the envelope glycoproteins, hemagglutinin and neuraminidase, are synthesized and incorporated into the plasma membrane [15].
• Organization and neuraminidase susceptibility of sialic acid residues in human melanoma cell lines with different heterotransplantabilities in nude mice [16].
• IRIV were prepared by combining phosphatidylcholine, phosphatidylethanolamine, phospholipids originating from the influenza virus envelope, influenza virus hemagglutinin, and neuraminidase [17].

Biological context of Neu1

• Here we report the identification in SM/J mice of a single amino acid substitution (L209I) in the Neu-1 protein which is responsible for the partial deficiency of lysosomal neuraminidase [18].
• A point mutation in the neu-1 locus causes the neuraminidase defect in the SM/J mouse [18].
• Analysis of the congenic strains revealed identical low activity (SM/J-type: Neu-1a/Neu-1a) NEU-1 phenotypes in all three strains [19].
• Gene for neuraminidase activity on mouse chromosome 17 near h-2: pleiotropic effects on multiple hydrolases [20].
• The low activity of liver neuraminidase that is characteristic of mouse strain SM/J is inherited as a single gene on chromosome 17, near the major histocompatibility complex [20].

Anatomical context of Neu1

• Neu1 infused alone or co-administered with its associated protein, protective protein/cathepsin A (PPCA) was effectively taken up by resident macrophages in many tissues [2].
• Cloning of the cDNA and gene encoding mouse lysosomal sialidase and correction of sialidase deficiency in human sialidosis and mouse SM/J fibroblasts [21].
• Northern blot analysis revealed high expression of multiple sialidase transcripts in kidney and epididymis, moderate levels in brain and spinal cord, and low levels in adrenal, heart, liver, lung and spleen [21].
• Identification and expression of NEU3, a novel human sialidase associated to the plasma membrane [22].
• A reduction of 70% of the plasma membrane-associated sialidase Neu3 activity, due to a corresponding reduction of the enzyme expression by transducing cells with a short hairpin RNA encoding a sequence target (complementary messenger of mouse Neu3), caused neurite elongation in Neuro2a murine neuroblastoma cells [4].

Associations of Neu1 with chemical compounds

• The Neu1 locus, in the S region of the murine histocompatibility-2 complex, regulates the sialic acid content of several liver lysosomal enzymes [23].
• The cDNA for this sialidase encodes a 428-residue protein containing a putative transmembrane helix, a YRIP (single-letter amino acid codes) motif and three Asp boxes characteristic of sialidases [22].
• These studies have indicated important roles for the neuraminidase (NA), matrix (M), non-structural (NS) and haemagglutinin (HA) genes of the virus in determining neurovirulence [24].
• The differences in charge heterogeneity of class I molecules between activated T-cells and the other cell subpopulations were abolished by treatment with: (1) endoglycosidase F which removes N-linked oligosaccharides from glycoproteins, and (2) neuraminidase which removes sialic acids from carbohydrate side chains [25].
• NEU1 lacks a functional mannose-6-phosphate recognition marker and is not endocytosed by mammalian cells [2].

Physical interactions of Neu1

• Protective protein/cathepsin A (PPCA) is a pleiotropic lysosomal enzyme that complexes with beta-galactosidase and neuraminidase, and possesses serine carboxypeptidase activity [26].
• Treatment of WEHI-3B cells with trypsin or neuraminidase abolished their ability to interact with P-selectin [27].
• Neuraminidase treatment of B8 cells did not affect the specific binding of erythropoietin, but tunicamycin treatment caused a 2.5 to 4-fold increase in the amount of 125I-erythropoietin binding [28].
• Class I major histocompatibility complex-restricted cytotoxic T lymphocytes (CTL) that recognize the neuraminidase (NA) glycoprotein of subtype N1 influenza A viruses have been demonstrated in BALB/c mice [29].
• A rapid and sensitive sialidase assay method based on peroxidase-labeled peanut lectin (PNA) binding to desialylated erythrocyte is described [30].

Co-localisations of Neu1

• In response to EGF, the sialidase redistributed rapidly to ruffling cell membranes of squamous carcinoma A431 cells and co-localized with Rac-1 [31].

Regulatory relationships of Neu1

• Epidermal growth factor-induced mobilization of a ganglioside-specific sialidase (NEU3) to membrane ruffles [31].
• Our present studies have characterized responsible sialoconjugate targets of Neu-1 and questioned possible biochemical mechanisms responsible for their regulatory influences on IL-4 gene expression [32].
• Neuraminidase-treated macrophages stimulate allogenic CD8+ T cells in the presence of exogenous interleukin 2 [33].
• E-selectin dependent adhesion of HL60 cells to HCMEC was blocked by neuraminidase, but not by NaClO3 and returned to control levels within 18 hours of HCMEC stimulation [34].
• The trans-sialidase-induced apoptosis proceeds through the TNF-alpha receptor 1 deathly signaling leading to the activation of the caspase 3 [35].

Other interactions of Neu1

• Evidence for placing the Neu-1 locus within the mouse H-2 complex [36].
• This indicates that Neu-1 lies in the segment of the SM/J-derived H-2 region that is common to all three strains: H-2E alpha to H-2D [19].
• The pathologic manifestations in patients relate primarily to the severe deficiency of neuraminidase, and the physiological significance of cathepsin A activity remains unclear [37].
• We discussed the possibility that the M1 protein helped the NA protein in its role to modify the HA protein on the cell surface [5].
• The gene order and map distances in per cent recombination of the loci studied are T (20.6 +/- 3.4) Pgk-2 (7.4 +/- 2.2) Apl [38].

Analytical, diagnostic and therapeutic context of Neu1

• We here explored functional subcellular localization of the sialidase by immunofluorescence and found accumulation at leading edges of cell membranes in the presence of serum in culture [31].
• Immunoprecipitation experiments showed the GR antigen to be 110-120 kD Mr. The binding of soluble GR antigen was inhibited by EDTA and O-sialoglycoprotease, but not neuraminidase treatment of the target cells [39].
• Pretreatment of RBMM with trypsin prevented rosette formation, but neuraminidase enhanced it [40].
• Failure of immunotherapy with neuraminidase-treated tumor cell vaccine in mice bearing established 3-methylcholanthrene-induced sarcomas [41].
• The B2 chain protein was not secreted by the cells; rather it could be detected on the cell surface after treatment of cells with neuraminidase [42].

References