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Cited by 185Cellular transport and secretionGlycosylation and Glycoproteins ResearchLysosomal Storage Disorders Research

Neuraminidase 1 Is a Negative Regulator of Lysosomal Exocytosis

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Yogalingam, Gouri, Bonten, Erik J., van de Vlekkert, Diantha, Hu, Huimin, Moshiach, Simon, Connell, Samuel A., d'Azzo, Alessandra·2008·Developmental Cell
DOI 10.1016/j.devcel.2008.05.005PMC PMC2664108
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Abstract

Lysosomal exocytosis is a Ca2+-regulated mechanism that involves proteins responsible for cytoskeletal attachment and fusion of lysosomes with the plasma membrane. However, whether luminal lysosomal enzymes contribute to this process remains unknown. Here we show that neuraminidase NEU1 negatively regulates lysosomal exocytosis in hematopoietic cells by processing the sialic acids on the lysosomal membrane protein LAMP-1. In macrophages from NEU1-deficient mice, a model of the disease sialidosis, and in patients' fibroblasts, oversialylated LAMP-1 enhances lysosomal exocytosis. Silencing of LAMP-1 reverts this phenotype by interfering with the docking of lysosomes at the plasma membrane. In neu1-/- mice the excessive exocytosis of serine proteases in the bone niche leads to inactivation of extracellular serpins, premature degradation of VCAM-1, and loss of bone marrow retention. Our findings uncover an unexpected mechanism influencing lysosomal exocytosis and argue that exacerbations of this process form the basis for certain genetic diseases.

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  • Lysosomal exocytosis secretes lysosomal contents, including Aβ peptides and active enzymes, into the extracellular space.

    “Additionally, we find that Neu1 dysregulation leads to a marked increase in lysosomal exocytosis, a mechanism through which lysosomal contents, including Aβ peptides and active enzymes, are secreted into the extracellular space 35,38,39 .”

    From Targeting Lysosomal Dysfunction to Alleviate Plaque Deposition in an Alzheimer Disease Model (2025) · cites this paper as [35]

    The Introduction describes lysosomal exocytosis as expelling lysosomal contents, and the Results section on Neu1-/- mice reports extracellular release of active lysosomal hydrolases. Our copy does not identify Aβ peptides among the released contents, so that specific example is not supported by this source. (LLM, conf=0.88)

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Authors
Yogalingam, G., Bonten, E. J., van de Vlekkert, D., Hu, H., Moshiach, S., Connell, S. A., & d'Azzo, A.
Affiliations
St. Jude Children's Research Hospital (US)
ORCID
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2008-07
Volume
15
Issue
1
Pages
74-86
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/j.devcel.2008.05.005
PMC
PMC2664108
OpenAlex
W2041274762
Cited by
185
References
0
Citations by year
2026: 8 · 2025: 12 · 2024: 22 · 2023: 11 · 2022: 13 · 2021: 10 · 2020: 11 · 2019: 11 · 2018: 12 · 2017: 4 · 2016: 9 · 2015: 8 · 2014: 8 · 2013: 11 · 2012: 11
FWCI
3.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (DK52025, GM60905)
  • Assisi Foundation of Memphis
  • American Lebanese Syrian Associated Charities
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Keywords
lysosomal exocytosis, LAMP1, sialidosis, hematopoietic cells, macrophages, bone niche, serine protease, lysosomal enzymes
MeSH terms
Animals, Bone Marrow Cells, Cell Membrane, Cells, Cultured, Disease Models, Animal, Exocytosis, Fibroblasts, Gene Expression Regulation, Humans, Lysosomes, Macrophages, Models, Biological, Mucolipidoses, Neuraminidase, Stem Cells, Substrate Specificity, Mice, Knockout, Mice, Lysosomal-Associated Membrane Protein 1

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