Versatility of gasdermin D beyond pyroptosis

Area of Science:

• Cell Biology
• Immunology
• Molecular Biology

Background:

• Gasdermin D (GSDMD) is known for its role in pyroptosis, a pro-inflammatory cell death pathway.
• The N-terminal fragment (NT-p30) of GSDMD forms pores, traditionally linked to pyroptosis.

Purpose of the Study:

• To review the emerging evidence on the multifaceted roles of Gasdermin D beyond pyroptosis.
• To highlight the pleiotropic functions of GSDMD in both cell death and homeostasis.

Main Methods:

• Literature review of recent studies on Gasdermin D function.
• Analysis of experimental data investigating GSDMD's involvement in various cellular processes.

Main Results:

• GSDMD-NT pore formation is demonstrated to be reversible.
• GSDMD activation is not exclusively tied to pyroptosis, suggesting alternative cell death or survival pathways.
• GSDMD participates in inflammation regulation, endolysosomal pathway rewiring, granule exocytosis, type II immunity, and food tolerance.

Conclusions:

• Gasdermin D exhibits a broader range of functions than previously understood.
• GSDMD's role extends to maintaining cellular homeostasis and regulating diverse physiological processes.
• Further research into GSDMD's pleiotropic nature is warranted.