Journal article
Bi-allelic mutations in STXBP2 reveal a complementary role for STXBP1 in cytotoxic lymphocyte killing
JA Lopez, T Noori, A Minson, LL Jovanoska, K Thia, MS Hildebrand, H Akhlaghi, PK Darcy, MH Kershaw, NJ Brown, A Grigg, JA Trapani, I Voskoboinik
Frontiers in Immunology | FRONTIERS MEDIA SA | Published : 2018
Abstract
The ability of cytotoxic lymphocytes (CL) to eliminate virus-infected or cancerous target cells through the granule exocytosis death pathway is critical to immune homeostasis. Congenital loss of CL function due to bi-allelic mutations in PRF1, UNC13D, STX11, or STXBP2 leads to a potentially fatal immune dysregulation, familial haemophagocytic lymphohistiocytosis (FHL). This occurs due to the failure of CLs to release functional pore-forming protein perforin and, therefore, inability to kill the target cell. Bi-allelic mutations in partner proteins STXBP2 or STX11 impair CL cytotoxicity due to failed docking/fusion of cytotoxic secretory granules with the plasma membrane. One unique feature o..
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Awarded by National Science Foundation
Funding Acknowledgements
This work was supported by National Health and Medical Research Council of Australia project grant 1062990 and fellowship 1059126 (to IV).