Spatial compartmentalization of signaling modules is an important aspect of signal transduction in cells. In Science Signaling, Sarin and colleagues describe that cytoplasmic localization of the Notch intracellular domain (NIC) and its association with the PI3 kinase and the mTORC2 component Rictor protect Treg cells, but not effector T cells, from apoptosis triggered by cytokine withdrawal. NIC has a predominantly cytoplasmic distribution in natural Treg cells, but not in effector T cells or induced Treg cells, and this correlates with resistance to apoptosis. The cytoplasmic localization of NIC is dependent on TCR engagement and Notch-ligand interactions but is independent of the transcriptional activity of NIC. Expression of the Notch ligand Delta-like 1 on Treg cells is required for this survival effect in culture, whereas the source of Notch ligands in the physiological context of Treg cell function remains unclear.

Sci. Signal. (24 July 2012) doi:10.1126/scisignal.2002859