Recombinant Mouse Gasdermin-A3 (Gsdma3), partial

Function

Pore-forming protein that causes membrane permeabilization and pyroptosis (PubMed:26375003, PubMed:27281216, PubMed:35545613). Released upon cleavage by some bacterial effector protein, and binds to membrane inner leaflet lipids (By similarity). Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the release of mature interleukin-1 (IL1B and IL18) and triggering pyroptosis (PubMed:27281216, PubMed:33883744, PubMed:35545613). Binds to membrane inner leaflet lipids, including bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, as well as phosphatidylinositol (3,4,5)-bisphosphate, and more weakly to monophosphorylated phosphatidylinositols (PubMed:27281216). Also binds to bacterial and mitochondrial lipids, including cardiolipin, and exhibits bactericidal activity (PubMed:27281216, PubMed:29695864). Plays a role in the transition from catagen to telogen at the end of hair follicle morphogenesis, possibly by regulating hair follicle stem cell niche maintenance (PubMed:15475261, PubMed:15737203, PubMed:17572385, PubMed:22155111, PubMed:32302611). Also required for mammary gland development (PubMed:28168650)

Subcellular Location

Cell membrane (Multi-pass membrane protein); Mitochondrion membrane (Multi-pass membrane protein)

Tissue Specificity

Highest levels in skin with weak expression in placenta and testis. Not detected in the gastrointestinal tract. In skin, expressed in postnatal hair follicles and epidermis as well as sebaceous gland basal cells

Subunit

Homooligomer; homooligomeric ring-shaped pore complex containing 18-36 subunits when inserted in the membrane

• Runkel F. et al. The dominant alopecia phenotypes Bareskin, Rex-denuded, and Reduced Coat 2 are caused by mutations in gasdermin 3. — Genomics (2004)
• Church D.M. et al. Lineage-specific biology revealed by a finished genome assembly of the mouse. — PLoS Biol. (2009)
• Tamura M. et al. Members of a novel gene family, Gsdm, are expressed exclusively in the epithelium of the skin and gastrointestinal tract in a highly tissue-specific manner. — Genomics (2007)
• Lunny D.P. et al. Mutations in gasdermin 3 cause aberrant differentiation of the hair follicle and sebaceous gland. — J. Invest. Dermatol. (2005)
• Tanaka S. et al. A new Gsdma3 mutation affecting anagen phase of first hair cycle. — Biochem. Biophys. Res. Commun. (2007)
• Zhou Y. et al. Gsdma3 mutation causes bulge stem cell depletion and alopecia mediated by skin inflammation. — Am. J. Pathol. (2012)
• Kumar S. et al. Gsdma3(I359N) is a novel ENU-induced mutant mouse line for studying the function of Gasdermin A3 in the hair follicle and epidermis. — J. Dermatol. Sci. (2012)
• Shi P. et al. Loss of conserved Gsdma3 self-regulation causes autophagy and cell death. — Biochem. J. (2015)