The N Terminal Fragement Of Gasdermin D Could Form Oligomers And Migrates To The Plasma Membrane In Pyroptosis

Inflammasome is a functional protein complexes,which plays an important role in innate immunity.Inflammation can activate the activity of caspasel，then cut GSDMD and IL-1βand IL-18,which can induced pyroptosis and cytokine secretion respectively.They both have a hand in innate immunity,the disorders of pyroptosis and the abnormal activation of inflammasome will lead to a variety of autoimmune diseases.Pyroptosis is a new defined programmed cell death,the discovery of GSDMD is one of the greatest progress in the study of pyroptosis.After processed by caspase1/caspasell,GSDMD would induce pyroptosis.However,the mechanism of how GSDMD execute pyroptosis has not been reported yet.In this paper,we verified the functional mechanism of GSDMD protein in vivo and in vitro.Finding that the N-terminal fragment of GSDMD(GSDMD-N)generated by caspase cleavage could forms oligomer and migrates to the plasma membrane to kill cells in pyroptosis.It is the ability that GSDMD-N can forms non-selective pores on the plasma membrane,does GSDMD mediate the plasma membrane rupture,finally induced cell death.It is known that the execution of necroptosis is mediated by mixed lineage kinase domain-like(MLKL)oligomers in the plasma membrane,and MLKL also can translocate to the plasma membrane to form ion channel during necroptosis.This paper compares the similarities and differences between two cell death executor GSDMD and MLKL.