Gasdermin family proteins as a permeabilization factor of cell membrane in pyroptosis process

Abstract

The type of cell death, i.e. apoptosis, autophagy, necrosis or pyroptosis, depends on the inducing factor and the phase of the cell cycle. The main role in immunological response to microorganisms is played by a process called pyroptosis. Pyroptosis induces various types of inflammatory factors in response to molecular patterns associated with pathogens, e.g., bacterial lipopolysaccharide in the canonical or non-canonical pathway depending on the type of caspases involved. In pyroptosis, the gasdermin D protein belonging to the gasdermin protein family (A, B, C, D, E and DFNB59) plays an important role, which is characterized by specific tissue gene expression mainly in epithelial cells, skin and the digestive system and is responsible for regulating the proliferation and differentiation of cells and is responsible for inhibiting or developing cancers in various organs. The GSDM family is responsible for the formation of pores in the cell membrane, enabling the secretion of proinflammatory cytokines (IL-1β and IL-18) involved in initiating inflammatory response pathways by recruiting and activating immune cells at the site of infection. The gasdermin D protein plays an essential role in the non-canonical pyroptosis process, whose N-terminal forming pores in the cell membrane leads to edema, osmotic lysis and, consequently, to the death of the infected cell.