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CD44 binds a chondroitin sulfate proteoglycan, aggrecan
T Fujimoto1, H Kawashima, T Tanaka
1Department of Bioregulation, Biomedical Research Center, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan.
International Immunology
|February 27, 2001
Summary
CD44 binds to aggrecan, a key cartilage component, via its chondroitin sulfate chains. This interaction mediates cell adhesion and may trigger intracellular signaling by inducing CD44 molecule oligomerization.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- CD44 is a cell surface glycoprotein involved in cell adhesion and signaling.
- Aggrecan is a major proteoglycan in cartilage, essential for its structural integrity.
Purpose of the Study:
- To investigate the binding interaction between CD44 and aggrecan.
- To elucidate the role of chondroitin sulfate (CS) side chains in CD44-aggrecan binding.
- To explore the functional consequences of CD44-aggrecan interaction.
Main Methods:
- Immunoassays using immobilized aggrecan and CD44-IgG or CD44(+) cells.
- Enzymatic digestion of aggrecan with chondroitinase, hyaluronidase, and keratanase.
- Analysis of glycosaminoglycan composition (CS A, CS C).
- Functional assays using CD44-Fas chimeric molecules and anti-CD44 antibodies.
Main Results:
- CD44 directly binds to aggrecan through its chondroitin sulfate (CS) side chains.
- Binding is dependent on CS A and CS C, but not hyaluronic acid.
- The CD44-aggrecan interaction can induce apoptosis in cells expressing CD44-Fas chimeric molecules.
- This interaction suggests potential for CD44 molecule oligomerization and subsequent intracellular signaling.
Conclusions:
- CD44 interacts with aggrecan via CS moieties, mediating cell adhesion.
- The CD44-aggrecan interaction can trigger CD44 oligomerization, potentially initiating intracellular signaling pathways.
- These findings highlight a novel mechanism for cell-matrix communication in cartilage.