Integrin bidirectional signaling: a molecular view

Abstract

Cells receive and send signals across the plasma membrane using the integrin family of receptors. What is it about their structure that can mediate their function?

Figure 1. A Model for Integrin Inside-Out Activation and Clustering

Cellular stimulation induces a conformational change in talin that exposes its talin head domain. The talin head domain binds to the β cytoplasmic tail, which displaces the α tail from its complex with the β tail, which in turn leads to an unclasping and a membrane-associated structural change of the cytoplasmic face (Vinogradova et al. 2002, 2004). Notice the proposed shifted membrane interface for both membrane-proximal helices before and after unclasping (green bars), which suggests a “fanning-out” unclasping process (Vinogradova et al. 2004). The unclasping initiates the opening of the integrin C-terminal stalks—including the transmembrane domains (Luo et al. 2004)—which is necessary for the switchblade shift of the extracellular headpiece from the bent to the extended form for high-affinity ligand binding (Takagi et al. 2002). The α subunit is in blue and the β subunit is in red. The ligated integrins cluster, possibly via oligomerization of transmembrane domains (Li et al. 2003). The model was generated based on the crystal structure of α_vβ₃ extracellular domain (Xiong et al. 2001) and the nuclear magnetic resonance structure of the cytoplasmic domain (Vinogradova et al. 2002, 2004) with the helices extending to the transmembrane domain.