title: NAD-induced T cell death: ADP-ribosylation of cell surface proteins by ART2 activates the cytolytic P2X7 purinoceptor.
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.
authors.affiliation: Université Denis Diderot, F-75251 Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Seman
authors.forename: Sahil
authors.initials: S
authors.lastname: Adriouch
authors.forename: Felix
authors.initials: F
authors.lastname: Scheuplein
authors.forename: Christian
authors.initials: C
authors.lastname: Krebs
authors.forename: Dunja
authors.initials: D
authors.lastname: Freese
authors.forename: Gustavo
authors.initials: G
authors.lastname: Glowacki
authors.forename: Phillipe
authors.initials: P
authors.lastname: Deterre
authors.forename: Friedrich
authors.initials: F
authors.lastname: Haag
authors.forename: Friedrich
authors.initials: F
authors.lastname: Koch-Nolte
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D058851:GPI-Linked Proteins; D019041:L-Selectin / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009243:NAD / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D058851:GPI-Linked Proteins; D008565:Membrane Proteins; C546468:P2RX7 protein, human; C546469:P2rx7 protein, mouse; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D009243:NAD; D019041:L-Selectin; D036002:ADP Ribose Transferases; C449301:ART1 protein, human; D002118:Calcium