Integrin receptors engage in inside out signalling necessary for calibrating the cells’ response to the external chemical and physical world. Here we show that upon ligation, intergin receptors reorganize their immediate membrane milieu by the creation of nanoclusters of GPI-anchored proteins in the vicinity of the activated receptors. This generates a specialized membrane microenvironment necessary for the functioning of the integrin receptor. While an understanding of the physico-chemical principles behind the generation of these nanoclusters via the active mechanics of actin filaments and myosin is emerging (1, 2), the ability to trigger these nanoclusters via integrin-mediated signalling has allowed a dissection of the molecular machinery required for the nanoclustering of GPI-APs. In my talk I will discuss our current understanding of the mechanism behind GPI-AP nanoclustering, and how this is necessary for mediating membrane receptor function, in the context of specific-integrin-dependent cell responses.
1) Gowrishankar, K., et al. (2012). Active remodeling of cortical actin regulates spatiotemporal organization of cell surface molecules. Cell 149, 1353–1367.
2) Raghupathy, R., , et al. (2015). Transbilayer Lipid Interactions Mediate Nanoclustering of Lipid-Anchored Proteins. Cell 161, 581–594.