title: Cutting edge: a natural P451L mutation in the cytoplasmic domain impairs the function of the mouse P2X7 receptor.
abstract: The P2X7 receptor (P2X(7)R) is an ATP-gated channel that mediates apoptosis of cells of the immune system. The capacity of P2X(7)R to form large pores depends on its large cytoplasmic tail, which harbors a putative TNFR-related death domain. Previous transfection studies indicated that mouse P2X(7)R forms pores much less efficiently than its counterparts from humans and rats. In this study, we demonstrate that an allelic mutation (P451L) in the predicted death domain of P2X(7)R confers a drastically reduced sensitivity to ATP-induced pore formation in cells from some commonly used strains of mice, i.e., C57BL/6 and DBA/2. In contrast, most other strains of mice, including strains derived from wild mice, carry P451 at this position as do rats and humans. The effects of the P451L mutation resemble those of the E496A mutation in human P2X(7)R. These P2X(7)R mutants may provide useful tools to decipher the molecular mechanisms leading to pore formation.
authors.affiliation: Université Denis Diderot, Paris, France.
authors.forename: Sahil
authors.initials: S
authors.lastname: Adriouch
authors.forename: Claudia
authors.initials: C
authors.lastname: Dox
authors.forename: Vivienne
authors.initials: V
authors.lastname: Welge
authors.forename: Michel
authors.initials: M
authors.lastname: Seman
authors.forename: Friedrich
authors.initials: F
authors.lastname: Koch-Nolte
authors.forename: Friedrich
authors.initials: F
authors.lastname: Haag
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007930:Leucine / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009154:Mutation; D010718:Phosphatidylserines / Q000494:pharmacology; D011392:Proline / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058486:Receptors, Purinergic P2X7; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism
chemical_list: C546468:P2RX7 protein, human; C546469:P2rx7 protein, mouse; D010718:Phosphatidylserines; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D011392:Proline; D007930:Leucine; D002118:Calcium