Disruption of focal adhesions mediates detachment during neuronal apoptosis

Apoptosis participates in the development of the nervous system and in neur odegeneration. The aim of this study was to investigate the mechanisms of d etachment of neuronal cells from the extracellular matrix (ECM) during apop tosis. Detachment of Ntera2 neuronal cells was accompanied by decreased sur face expression of the beta1 integrin and redistribution of proteins from f ocal adhesions (FA). FA proteins were cleaved in a discrete sequence: p130c as, then paxillin, then talin. Caspase inhibition prevented detachment and cleavage of paxillin and p130cas, whilst calpain inhibition blocked talin c leavage. Neuronal cells therefore detach as a result of redistribution and caspase-dependent cleavage of focal adhesion proteins. Cleavage occurs sequ entially such that critical ECM-integrin survival signalling cascades are s evered before disruption of focal adhesion-cytoskeletal links: NeuroReport 12:2111-2115 (C) 2001 Lippincott Williams & Wilkins.