Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly.

Integrin receptor activation initiates the formation of integrin adhesion complexes (IACs) at the cell membrane that transduce adhesion-dependent signals to control a multitude of cellular functions. Proteomic analyses of isolated IACs have revealed an unanticipated molecular complexity; however, a global view of the consensus composition and dynamics of IACs is lacking. Here, we have integrated several IAC proteomes and generated a 2,412-protein integrin adhesome.

A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting.

Integrin activation, which is regulated by allosteric changes in receptor conformation, enables cellular responses to the chemical, mechanical and topological features of the extracellular microenvironment. A global view of how activation state converts the molecular composition of the region proximal to integrins into functional readouts is, however, lacking. Here, using conformation-specific monoclonal antibodies, we report the isolation of integrin activation state-dependent complexes and their characterization by mass spectrometry.

Mapping the ligand-binding pocket of integrin alpha5beta1 using a gain-of-function approach.

Integrin alpha5beta1 is a key receptor for the extracellular matrix protein fibronectin. Antagonists of human integrin alpha5beta1 have therapeutic potential as anti-angiogenic agents in cancer and diseases of the eye. However, the structure of the integrin is unsolved and the atomic basis of fibronectin and antagonist binding by integrin alpha5beta1 is poorly understood.