Tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin.

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Biology

Background:

• Tissue transglutaminase (TG2) is a known enzyme involved in protein cross-linking.
• Fibronectin is a key extracellular matrix protein mediating cell adhesion.
• Integrins are crucial cell surface receptors that bind extracellular matrix components.

Purpose of the Study:

• To investigate the role of cell surface tissue transglutaminase in cell adhesion and spreading.
• To determine the mechanism by which tissue transglutaminase interacts with fibronectin and integrins.
• To elucidate the functional significance of tissue transglutaminase-integrin interactions.

Main Methods:

• Cell culture and adhesion assays.
• Overexpression of tissue transglutaminase.
• Western blotting and immunofluorescence microscopy.
• Co-immunoprecipitation to detect protein interactions.

Main Results:

• Cell surface tissue transglutaminase mediates cell adhesion and spreading on fibronectin, independent of integrin-binding motifs.
• Overexpression of tissue transglutaminase enhances cell adhesion, focal adhesion formation, and focal adhesion kinase phosphorylation.
• Tissue transglutaminase directly interacts with beta1 and beta3 integrins, forming stable complexes that accumulate at focal adhesions.
• The adhesive function of tissue transglutaminase does not require its enzymatic cross-linking activity.

Conclusions:

• Tissue transglutaminase functions as an integrin-associated coreceptor, bridging integrins to fibronectin.
• This interaction promotes cell adhesion and spreading, highlighting a novel role for TG2 beyond its enzymatic activity.
• The findings reveal a new mechanism for regulating cell-matrix interactions via TG2-integrin complexes.