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Exploration into Galectin-3 Driven Endocytosis and Lattices

Shafaq-Zadah, Massiullah ; Dransart, Estelle ; Mani, Satish Kailasam ; Sampaio, Julio Lopes ; Bouidghaghen, Lydia ; Nilsson, Ulf J. LU ; Leffler, Hakon LU and Johannes, Ludger (2024) In Biomolecules 14(9).
Abstract
Essentially all plasma membrane proteins are glycosylated, and their activity is regulated by tuning their cell surface dynamics. This is achieved by glycan-binding proteins of the galectin family that either retain glycoproteins within lattices or drive their endocytic uptake via the clathrin-independent glycolipid-lectin (GL-Lect) mechanism. Here, we have used immunofluorescence-based assays to analyze how lattice and GL-Lect mechanisms affect the internalization of the cell adhesion and migration glycoprotein α5β1 integrin. In retinal pigment epithelial (RPE-1) cells, internalized α5β1 integrin is found in small peripheral endosomes under unperturbed conditions. Pharmacological compounds were... (More)
Essentially all plasma membrane proteins are glycosylated, and their activity is regulated by tuning their cell surface dynamics. This is achieved by glycan-binding proteins of the galectin family that either retain glycoproteins within lattices or drive their endocytic uptake via the clathrin-independent glycolipid-lectin (GL-Lect) mechanism. Here, we have used immunofluorescence-based assays to analyze how lattice and GL-Lect mechanisms affect the internalization of the cell adhesion and migration glycoprotein α5β1 integrin. In retinal pigment epithelial (RPE-1) cells, internalized α5β1 integrin is found in small peripheral endosomes under unperturbed conditions. Pharmacological compounds were used to competitively inhibit one of the galectin family members, galectin-3 (Gal3), or to inhibit the expression of glycosphingolipids, both of which are the fabric of the GL-Lect mechanism. We found that under acute inhibition conditions, endocytic uptake of α5β1 integrin was strongly reduced, in agreement with previous studies on the GL-Lect driven internalization of the protein. In contrast, upon prolonged inhibitor treatment, the uptake of α5β1 integrin was increased, and the protein was now internalized by alternative pathways into large perinuclear endosomes. Our findings suggest that under these prolonged inhibitor treatment conditions, α5β1 integrin containing galectin lattices are dissociated, leading to an altered endocytic compartmentalization. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Endocytosis, Humans, Galectin 3/metabolism, Integrin alpha5beta1/metabolism, Cell Line, Endosomes/metabolism, Cell Adhesion, Galectins/metabolism, Blood Proteins
in
Biomolecules
volume
14
issue
9
article number
1169
pages
20 pages
publisher
MDPI AG
external identifiers
  • pmid:39334935
  • scopus:85205125391
ISSN
2218-273X
DOI
10.3390/biom14091169
language
English
LU publication?
yes
id
276bcac6-73cf-485f-a3a6-bfe2e787bae5
date added to LUP
2024-10-03 16:33:46
date last changed
2025-07-12 05:34:12
@article{276bcac6-73cf-485f-a3a6-bfe2e787bae5,
  abstract     = {{Essentially all plasma membrane proteins are glycosylated, and their activity is regulated by tuning their cell surface dynamics. This is achieved by glycan-binding proteins of the galectin family that either retain glycoproteins within lattices or drive their endocytic uptake via the clathrin-independent glycolipid-lectin (GL-Lect) mechanism. Here, we have used immunofluorescence-based assays to analyze how lattice and GL-Lect mechanisms affect the internalization of the cell adhesion and migration glycoprotein α<sub>5</sub>β<sub>1</sub> integrin. In retinal pigment epithelial (RPE-1) cells, internalized α<sub>5</sub>β<sub>1</sub> integrin is found in small peripheral endosomes under unperturbed conditions. Pharmacological compounds were used to competitively inhibit one of the galectin family members, galectin-3 (Gal3), or to inhibit the expression of glycosphingolipids, both of which are the fabric of the GL-Lect mechanism. We found that under acute inhibition conditions, endocytic uptake of α<sub>5</sub>β<sub>1</sub> integrin was strongly reduced, in agreement with previous studies on the GL-Lect driven internalization of the protein. In contrast, upon prolonged inhibitor treatment, the uptake of α<sub>5</sub>β<sub>1</sub> integrin was increased, and the protein was now internalized by alternative pathways into large perinuclear endosomes. Our findings suggest that under these prolonged inhibitor treatment conditions, α<sub>5</sub>β<sub>1</sub> integrin containing galectin lattices are dissociated, leading to an altered endocytic compartmentalization.}},
  author       = {{Shafaq-Zadah, Massiullah and Dransart, Estelle and Mani, Satish Kailasam and Sampaio, Julio Lopes and Bouidghaghen, Lydia and Nilsson, Ulf J. and Leffler, Hakon and Johannes, Ludger}},
  issn         = {{2218-273X}},
  keywords     = {{Endocytosis; Humans; Galectin 3/metabolism; Integrin alpha5beta1/metabolism; Cell Line; Endosomes/metabolism; Cell Adhesion; Galectins/metabolism; Blood Proteins}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{9}},
  publisher    = {{MDPI AG}},
  series       = {{Biomolecules}},
  title        = {{Exploration into Galectin-3 Driven Endocytosis and Lattices}},
  url          = {{http://dx.doi.org/10.3390/biom14091169}},
  doi          = {{10.3390/biom14091169}},
  volume       = {{14}},
  year         = {{2024}},
}