Regulation of integrin

Keywords: AMPK, integrin activity, matrix remodelling, Ras-association domain, RNAi screens, SHANK, SHARPIN, talin, tensin

Introduction: Integrin heterodimers can exist in a bent/closed conformation with a low affinity for extracellular ligands (‘inactive’) or in an extended/open conformation with a high affinity for ligands (‘active’). As a consequence of this conformational switch, integrins are able to transmit signals bidirectionally across the cell membrane. Engagement of extracellular ligand by integrins elicits signalling responses within the cell (‘outside-in signalling), whereas binding of intracellular proteins such as talin and kindlins to the β-integrin tail (NPXY motifs) promote the ligand-binding receptor conformation (‘inside-out’ signalling).

Our research:  Our RNAi screens have thus far revealed several candidate proteins implicated in the regulation of integrin activity and importantly have led to the identification of SHARPIN, SHANKs and AMPK as negative regulators of integrin function (see Publications: Rantala et al., 2011; Lilja et al., 2017; Georgiadou et al., 2017 and below for a summary of these works).