Granulysin, also known as GNLY, is a protein which in humans is encoded by the GNLYgene. It is also known as NK-lysin after NK cells; the cattleortholog is sometimes referred to as Bo-lysin. Granulysin is released by cytotoxic T cells and NK cells when they are attached to infected body cells. It creates holes in the target cellmembrane and destroy it. Granulysin is able to induce apoptosis in target cells and also has antimicrobial action. Granulysin is broadly antimicrobial, killing microbes that cause, for example, tuberculosis and malaria, and can destroy some tumors. A series of peptides generated from the amino acid sequence of granulysin are potential antibiotics.
Function
Granulysin is a protein present in cytolytic granules of cytotoxic T cells and natural killer cells along with perforin and granzymes. Granulysin is a member of the saposin-like protein family and is released from cytotoxic T cells upon antigen stimulation. Granulysin has antimicrobial activity against M. tuberculosis and other organisms. Granulysin is alternatively spliced, resulting in the NKG5 and 519 transcripts. Granulysin is a cytolytic and proinflammatory molecule first identified by a subtractive hybridization screen for genes expressed “late” after activation of human peripheral blood mononuclear cells. Granulysin is present in cytolytic granules of cytotoxic T lymphocytes and natural killer cells. Granulysin is made as a 15 kD molecule, and a portion of it is cleaved at both the amino and carboxy termini into a 9 kD form. The 9 kD form is released by receptor-mediated granule exocytosis while the 15 kD form is constitutively secreted. Recombinant 9 kD granulysin is broadly cytolytic against tumors and microbes, including gram positive and gram negative bacteria, fungi/yeast and parasites. 9kD granulysin is also a chemoattractant for T lymphocytes, monocytes, and other inflammatory cells and activates the expression of a number of cytokines, including RANTES, MCP-1, MCP-3, MIP-1α, IL-10, IL-1, IL-6 and IFNα. Granulysin has been implicated in a myriad of diseases including infection, cancer, transplantation, autoimmunity, skin and reproductive maladies. Granulysin has recently been implicated in the development of Stevens–Johnson syndrome.
Evolution
GNLY orthologs have been identified in multiple species, including pigs, chicken, and cattle. Cattle has multiple copies of the gene with functional diversification. Mice do not have a granulysin homolog, but transgenic mice expressing human granulysin have been engineered.
