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Growth factor-triggered de-sialylation controls glycolipid-lectin-driven endocytosis

MacDonald, Ewan ; Forrester, Alison ; Valades-Cruz, Cesar A. ; Madsen, Thomas D. LU ; Hetmanski, Joseph H.R. ; Dransart, Estelle ; Ng, Yeap ; Godbole, Rashmi ; Shp, Ananthan Akhil and Leconte, Ludovic , et al. (2025) In Nature Cell Biology 27(3). p.449-463
Abstract

Glycolipid-lectin-driven endocytosis controls the formation of clathrin-independent carriers and the internalization of various cargos such as β1 integrin. Whether this process is regulated in a dynamic manner remained unexplored. Here we demonstrate that, within minutes, the epidermal growth factor triggers the galectin-driven endocytosis of cell-surface glycoproteins, such as integrins, that are key regulators of cell adhesion and migration. The onset of this process—mediated by the Na+/H+ antiporter NHE1 as well as the neuraminidases Neu1 and Neu3—requires the pH-triggered enzymatic removal of sialic acids whose presence otherwise prevents galectin binding. De-sialylated glycoproteins are then retrogradely... (More)

Glycolipid-lectin-driven endocytosis controls the formation of clathrin-independent carriers and the internalization of various cargos such as β1 integrin. Whether this process is regulated in a dynamic manner remained unexplored. Here we demonstrate that, within minutes, the epidermal growth factor triggers the galectin-driven endocytosis of cell-surface glycoproteins, such as integrins, that are key regulators of cell adhesion and migration. The onset of this process—mediated by the Na+/H+ antiporter NHE1 as well as the neuraminidases Neu1 and Neu3—requires the pH-triggered enzymatic removal of sialic acids whose presence otherwise prevents galectin binding. De-sialylated glycoproteins are then retrogradely transported to the Golgi apparatus where their glycan make-up is reset to regulate EGF-dependent invasive-cell migration. Further evidence is provided for a role of neuraminidases and galectin-3 in acidification-dependent bone resorption. Glycosylation at the cell surface thereby emerges as a dynamic and reversible regulatory post-translational modification that controls a highly adaptable trafficking pathway.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Cell Biology
volume
27
issue
3
article number
1457
pages
15 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:40000851
  • scopus:85218711814
ISSN
1465-7392
DOI
10.1038/s41556-025-01616-x
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s), under exclusive licence to Springer Nature Limited 2025.
id
f7e64f6c-2725-40a2-bd0c-200bf6781a27
date added to LUP
2025-07-04 09:23:23
date last changed
2025-07-07 07:50:24
@article{f7e64f6c-2725-40a2-bd0c-200bf6781a27,
  abstract     = {{<p>Glycolipid-lectin-driven endocytosis controls the formation of clathrin-independent carriers and the internalization of various cargos such as β1 integrin. Whether this process is regulated in a dynamic manner remained unexplored. Here we demonstrate that, within minutes, the epidermal growth factor triggers the galectin-driven endocytosis of cell-surface glycoproteins, such as integrins, that are key regulators of cell adhesion and migration. The onset of this process—mediated by the Na<sup>+</sup>/H<sup>+</sup> antiporter NHE1 as well as the neuraminidases Neu1 and Neu3—requires the pH-triggered enzymatic removal of sialic acids whose presence otherwise prevents galectin binding. De-sialylated glycoproteins are then retrogradely transported to the Golgi apparatus where their glycan make-up is reset to regulate EGF-dependent invasive-cell migration. Further evidence is provided for a role of neuraminidases and galectin-3 in acidification-dependent bone resorption. Glycosylation at the cell surface thereby emerges as a dynamic and reversible regulatory post-translational modification that controls a highly adaptable trafficking pathway.</p>}},
  author       = {{MacDonald, Ewan and Forrester, Alison and Valades-Cruz, Cesar A. and Madsen, Thomas D. and Hetmanski, Joseph H.R. and Dransart, Estelle and Ng, Yeap and Godbole, Rashmi and Shp, Ananthan Akhil and Leconte, Ludovic and Chambon, Valérie and Ghosh, Debarpan and Pinet, Alexis and Bhatia, Dhiraj and Lombard, Bérangère and Loew, Damarys and Larsen, Martin R. and Leffler, Hakon and Lefeber, Dirk J. and Clausen, Henrik and Blangy, Anne and Caswell, Patrick and Shafaq-Zadah, Massiullah and Mayor, Satyajit and Weigert, Roberto and Wunder, Christian and Johannes, Ludger}},
  issn         = {{1465-7392}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{449--463}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Cell Biology}},
  title        = {{Growth factor-triggered de-sialylation controls glycolipid-lectin-driven endocytosis}},
  url          = {{http://dx.doi.org/10.1038/s41556-025-01616-x}},
  doi          = {{10.1038/s41556-025-01616-x}},
  volume       = {{27}},
  year         = {{2025}},
}