The Plasma Membrane Na+/Ca2+ Exchanger Is Cleaved by Distinct Protease Families in Neuronal Cell Death


Address for correspondence: Dr. Daniele Bano, MRC Toxicology Unit, University of Leicester, Hodgkin Building, Lancaster Road LE1 9HN, Leicester, UK. Voice: +44-0116-2525571; fax: 0044 116 252 5616.


Abstract: Neurodegenerative conditions commonly involve loss of neuronal connectivity, synaptic dysfunction with excessive pruning, and ionic imbalances. These often serve as a prelude to cell death either through the activation of apoptotic or necrotic death routines or excess autophagy. In many instances, a local or generalized Ca2+ deregulation is involved in signaling or executing cell death. We have recently shown that in brain ischemia, and during excitotoxicity triggered by excess glutamate, the irreversible Ca2+ deregulation leading to necrosis is due to calpain-mediated modulation of the plasma membrane Na+/Ca2+ exchanger (NCX). Here we show that the NCX can also be cleaved by caspases in neurons undergoing apoptosis, which suggests that cleavage of the main Ca2+ extrusion pathway is a lethal event in multiple forms of cell death.