Effects on channel properties and induction of cell death induced by c-terminal truncations of pannexin1 depend on domain length.

摘要: Pannexin1 (Panx1) is an integral membrane protein and known to form multifunctional hexameric channels. Recently, Panx1 was identified be responsible for the release of ATP UTP from apoptotic cells after site-specific proteolysis by caspases 3/7. Cleavage at carboxy-terminal (CT) position aa 376–379 irreversibly opens human channels leads respective nucleotides resulting in recruitment macrophages subsequent activation immunologic response. The fact that cleavage CT this particular residues terminates a permanently open channel raised issue functional relevance regulating properties. To analyze impact on gating, we generated 14 truncated versions rat cleaved different positions C-terminus. This allowed elaboration influence defined formation, voltage-dependent execution cell mortality, susceptibility inhibitor carbenoxolone. We demonstrate expression proteins, which were lengths between 370 393 residues, induces differential effects Xenopus laevis oocytes as well Neuro2A with strongest downstream caspase 3/7 site.