Lysosomal Neuraminidase
Open accessAbstract
Lysosomal N-Acetyl-alpha-neuraminidase is active in complex with the protective protein/cathepsin A (PPCA) and beta-galactosidase. The interaction with PPCA is essential for the correct intracellular routing and lysosomal localization of neuraminidase, but the mechanism of its catalytic activation is unclear. To investigate this process, we have used the baculovirus expression system to co-express neuraminidase and PPCA precursors in insect cells, which resulted in high enzymatic activity of neuraminidase. Both the 34- and 20-kDa PPCA subunits were required for the activation. We further demonstrated that when expressed alone, the neuraminidase precursor remained dimeric (114 kDa) and had low enzymatic activity, but when co-expressed with PPCA and beta-galactosidase, it multimerized in a complex of approximately 1350 kDa, together with the other two proteins. The fully active neuraminidase co-precipitated with full-length PPCA and beta-galactosidase precursors. However, when co-expressed with the individual PPCA subunits, neuraminidase co-precipitated only with the small 20-kDa polypeptide, which therefore must contain a neuraminidase-binding site. Our finding suggests a model of activation of neuraminidase dependent on its oligomerization at acidic pH that is mediated by interaction with PPCA.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NEU1 and CTSA can associate into large complexes in the absence of GLB1.
“Accordingly, NEU1 and CTSA can also associate into large complexes in the absence of GLB1 (21, 22).”
From Structure of the immunoregulatory sialidase NEU1 (2023) · cites this paper as [22]
In the Baculovirus Expression in Insect section (page unavailable), neuraminidase formed an approximately 1350-kDa species when co-expressed with PPCA subunits without β-galactosidase (GLB1). But the PPCA subunits were not detected in those high-mass fractions; the authors say their association with neuraminidase may have been transient or below detection. The paper therefore supports large-complex formation without GLB1, but not clearly that both NEU1 and CTSA remain associated in those complexes. (LLM, conf=0.86)
Experimental — accuracy not yet measuredGLB1 is not necessary for NEU1 activity and may compete with NEU1 for access to CTSA.
“Whereas a third enzyme—the glycosidase GLB1—has often been reported as a member of the high–molecular weight NEU1-CTSA complex (15, 27), GLB1 is not necessary for NEU1 activity (12, 21–24, 27, 32) and may compete with NEU1 for access to CTSA (12, 32).”
From Structure of the immunoregulatory sialidase NEU1 (2023) · cites this paper as [22]
In the Results section (page not available), β-galactosidase/GLB1 had no effect on neuraminidase/NEU1 activity in the insect-cell experiments, supporting the claim that it was not necessary for activation in that setting. The paper also reports that all three proteins can associate, but the passages do not establish that GLB1 competes with NEU1 for access to PPCA/CTSA. (LLM, conf=0.84)
Experimental — accuracy not yet measuredCTSA is sufficient for NEU1 activity, whereas GLB1 is not necessary.
“However, CTSA is sufficient for NEU1 activity, whereas GLB1 is not necessary (12, 21–24, 27, 32).”
From Structure of the immunoregulatory sialidase NEU1 (2023) · cites this paper as [22]
NEU1 requires an accessory protein for activity-the protective protein cathepsin A (CTSA; PPCA).
“NEU1 is unique among all known mammalian, microbial, or viral sialidases, as it requires an accessory protein for activity—the protective protein cathepsin A (CTSA; PPCA) (12, 19–23).”
From Structure of the immunoregulatory sialidase NEU1 (2023) · cites this paper as [22]
NEU1 is unique among all known sialidases in that it requires an accessory protein for activity.
“NEU1 is unique among all known mammalian, microbial, or viral sialidases, as it requires an accessory protein for activity—the protective protein cathepsin A (CTSA; PPCA) (12, 19–23).”
From Structure of the immunoregulatory sialidase NEU1 (2023) · cites this paper as [22]
The reported 104-kDa heterodimeric complex does not match the large aggregates resulting in coprecipitation of both proteins or the megadalton-size complexes in vivo.
“This finding does not match the large aggregates resulting in coprecipitation of both proteins described above or the megadalton-size complexes in vivo (21, 22).”
From Structure of the immunoregulatory sialidase NEU1 (2023) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 5
- Andria, G., Strisciuglio, P., Pontarelli, G., Sly, W. S., and Dodson, W. E. (1981) in Sialidases and Sialidoses (Durand, P., Tettamanti, G., and DiDonato, S., eds), pp. 379 -395, Edizioni Ermes, Milan 5. d'Azzo, A., Andria, G., Strisciuglio, P., and Galjaard, H. (1995) in The Meta- bolic and Molecular Bases of Inherited Disease (Scriver, C., Beaudet, A., Sly, W., and Valle, D., eds) Vol. 2, 7th Ed., pp. 2825-2838, McGraw-Hill Pub- lishing Co., New York
- d'Azzo, A., Hoogeveen, A., Reuser, A. J., Robinson, D., and Galjaard, H. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 4535-4539
- Crennell, S. J., Garman, E. F., Laver, W. G., Vimr, E. R., and Taylor, G. L. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 9852-9856
- Braulke, T. (1996) Origin of Lysosomal Proteins (Mason, L. A., ed) Vol. 27, pp. 15-49, Plenum Press, New York
- Galjaard, H. (1980) Genetic Metabolic Diseases: Early Signs and Prenatal Analysis, p. 817, Elsevier, New York
Cited by
Sorted by citations
Annunziata, I., Patterson, A., Helton, D., Hu, H., Moshiach, S., Gomero, E., Nixon, R., & d’Azzo, A. (2013) · Nature Communications · doi:10.1038/ncomms3734 · Cited by 146 · see citing works
Self-citationStructure of the immunoregulatory sialidase NEU1
Gorelik, A., Illes, K., Mazhab-Jafari, M. T., & Nagar, B. (2023) · Science Advances · doi:10.1126/sciadv.adf8169 · Cited by 36 · see citing works
- Authors
- Bonten, E. J., & d'Azzo, A.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 275
- Issue
- 48
- Pages
- 37657-37663
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2089241378
- Cited by
- 51
- References
- 0
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 4
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Assisi Foundation of Memphis
- St. Jude Children's Research Hospital
- American Lebanese Syrian Associated Charities (CA 21765)
- National Institutes of Health (CA21765))
- National Cancer Institute (CA21765, P30CA021765)
- National Institute of General Medical Sciences (R01GM060950)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- beta-galactosidase, enzyme activation, protein-protein interaction, protein oligomerization, low pH, lysosomal localization, baculovirus expression system
- MeSH terms
- Animals, Carboxypeptidases, Catalysis, Cell Line, Enzyme Activation, Lysosomes, Neuraminidase, Spodoptera, Cathepsin A
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
