Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 19 (4), 571-82

NAD-induced T Cell Death: ADP-ribosylation of Cell Surface Proteins by ART2 Activates the Cytolytic P2X7 Purinoceptor

Affiliations

NAD-induced T Cell Death: ADP-ribosylation of Cell Surface Proteins by ART2 Activates the Cytolytic P2X7 Purinoceptor

Michel Seman et al. Immunity.

Abstract

T cells express a toxin-related ADP-ribosylating ectoenzyme, ART2. Exposure of mature T cells to NAD, the substrate for ADP-ribosylation, induces cell death. ART2-catalyzed ADP-ribosylation activates the cytolytic P2X7 purinoceptor, causing calcium flux, pore formation, phosphatidylserine exposure, shedding of CD62L, cell shrinkage, and propidium iodide uptake. Interestingly, much lower NAD than ATP concentrations are required to activate P2X7. NAD-induced cell death (NICD) operates with endogenous sources of NAD released upon cell lysis. These findings identify P2X7 as a key effector of NICD and demonstrate that P2X7 can be activated by an endogenous ligand other than ATP. Our results delineate an alternative mechanism for inducing T cell death and set an interesting precedent for immunoregulation via crosstalk between NAD-dependent ADP-ribosyltransferases and purinoceptors.

Similar articles

See all similar articles

Cited by 85 articles

See all "Cited by" articles

Publication types

Feedback