Collagen-binding integrin receptor

The collagen-binding integrin receptors, primarily comprising the alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1, and alpha-11/beta-1 heterodimers, serve as the primary mechanical and biochemical link between the extracellular matrix (ECM) and the intracellular environment (Zeltz & Gullberg, 2016). These receptors recognize specific triple-helical motifs in collagen through a specialized I-domain in the alpha subunit, facilitating bidirectional signaling known as 'inside-out' and 'outside-in' signaling (Leitinger, 2011). Biologically, they regulate essential processes including cell adhesion, migration, proliferation, and the remodeling of the ECM (McCall-Culbreath & Zutter, 2008). In pathological states, the system is frequently dysregulated; for instance, alpha-11/beta-1 is a key driver of myofibroblast differentiation in organ fibrosis, while alpha-2/beta-1 facilitates tumor cell metastasis and platelet aggregation (Borza & Pozzi, 2014). Therapeutic strategies targeting this system focus on small molecule antagonists and monoclonal antibodies that block collagen binding or inhibit the activation of the integrin (McCall-Culbreath & Zutter, 2008). However, drug development faces challenges due to the structural similarity between integrin subtypes and the potential for systemic side effects like impaired wound healing or bleeding.

Other names

Extracellular matrix / collagen-integrin systemCollagen-integrin axisCollagen-binding integrinsVLA-1VLA-2Integrin alpha-1 beta-1Integrin alpha-2 beta-1Integrin alpha-10 beta-1Integrin alpha-11 beta-1

Competitive or allosteric inhibition of the integrin alpha-subunit I-domain to prevent binding to collagen triple-helical motifs.