Related Experiment Video
Updated: Mar 16, 2026
06:56
Generating a Fractal Microstructure of Laminin-111 to Signal to Cells
Published on: September 28, 2020
1.4K
LARGE2-dependent glycosylation confers laminin-binding ability on proteoglycans
Kei-Ichiro Inamori1,2,3, Aaron M Beedle1,2,4, Daniel Beltrán-Valero de Bernabé1,2
1Department of Molecular Physiology and Biophysics, Howard Hughes Medical Institute, and.
Glycobiology
|August 7, 2016
Summary
The LARGE2 enzyme modifies proteoglycans with a specific glycan, enhancing their ability to bind laminin. This suggests LARGE2 has distinct roles in basement membrane function beyond modifying α-dystroglycan.
Area of Science:
- Biochemistry
- Glycobiology
- Cell Biology
Background:
- LARGE1 and LARGE2 are bifunctional glycosyltransferases synthesizing a [-3Xylα1,3GlcAβ1-] polymer.
- This polysaccharide modifies α-dystroglycan (α-DG) O-mannosyl glycan, crucial for extracellular matrix (ECM) ligand binding.
- While both LARGE paralogs contribute to α-DG modification, their distinct functional roles and substrates beyond α-DG remain unclear.
Purpose of the Study:
- To investigate the functional differences between LARGE1 and LARGE2.
- To determine if LARGE2 can modify substrates other than α-DG.
- To identify potential new roles for LARGE2 in ECM interactions.
Main Methods:
- Overexpression of LARGE2 in DG-/-, Pomt1-/-, and Fktn-/- embryonic stem cells.
- Affinity purification and mass spectrometry to identify LARGE2 substrates.
- Analysis of proteoglycan (PG) modification with the laminin-binding glycan.
Main Results:
- Overexpression of LARGE2, but not LARGE1, mediated functional modification on the surface of knockout cells.
- Glypican-4 was identified as a substrate for LARGE2-dependent modification.
- LARGE2 was shown to modify several other PGs with the laminin-binding glycan, likely in the GAG-protein linkage region.
Conclusions:
- LARGE2 can modify proteoglycans with a GAG-like polysaccharide, conferring laminin binding.
- This indicates LARGE2 has roles beyond α-DG modification, potentially impacting basement membrane stability.
- LARGE2 may augment ECM protein-PG interactions, influencing basement membrane function.
Related Concept Videos
00:55Laminins are the Adhesive Proteins of Basal Lamina
4.0K
Laminins are heterotrimeric proteins with high molecular mass found in the extracellular matrix. Each laminin molecule is composed of three chains, viz. alpha, beta, and gamma, coded by five, four, and three paralogous genes, respectively. Laminins are categories based on the compositions of the three chains.
In humans, the five forms of alpha chains are LAMA 1, LAMA 2, LAMA 3, LAMA 4, and LAMA 5. The four forms of beta chains are LAMB 1, LAMB 2, LAMB 3, and LAMB 4. The three forms of gamma...
In humans, the five forms of alpha chains are LAMA 1, LAMA 2, LAMA 3, LAMA 4, and LAMA 5. The four forms of beta chains are LAMB 1, LAMB 2, LAMB 3, and LAMB 4. The three forms of gamma...
4.0K
01:05Proteoglycans
5.1K
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
5.1K
01:21Matrix Proteoglycans and Glycoproteins
5.5K
Proteoglycans are extensively glycosylated proteins, commonly found in the extracellular matrix, interwoven with collagen fibers. Hyaline cartilage, the most common type of cartilage in the body, consists of short and dispersed collagen fibers associated with large amounts of proteoglycans. These proteoglycans have long negative charges that attract cations, which in turn attract water molecules. This influx of ions and water molecules swells up the proteoglycan like a water-soaked gel that can...
5.5K
01:25Protein Glycosylation
10.3K
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
10.3K
01:24Oligosaccharide Assembly
3.8K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
3.8K
01:23Glycosaminoglycans
7.5K
Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
7.5K