Environmental and Their Disruption of Integrin Signaling in Lipid Rafts.

Abstract

Talin, a key integrin activator, is essential for cellular adhesion, signal transduction, and mechanical stability. Its transition between autoinhibited and active conformations allows dynamic regulation of adhesion in response to environmental cues. Cholesterol-rich membrane microdomains, such as lipid rafts, organize and stabilize signaling platforms, influencing talin and integrin conformational states. Cholesterol is a switch modulating talin activation, integrin binding, and adhesion. Environmental pollutants, including heavy metals and air toxins, disrupt cholesterol homeostasis, destabilize lipid rafts, and interfere with talin-integrin interactions. These disruptions impair adhesion, tissue repair, and signaling fidelity, contributing to atherosclerosis and cancer metastasis. Understanding talin's interaction with cholesterol-rich domains offers critical insights into adhesion regulation and reveals the broader impact of environmental toxicants on cellular function. This framework emphasizes the importance of membrane composition, particularly cholesterol, in mediating the effects of environmental stressors and suggests potential therapeutic interventions.