Cutting edge: syntaxin 11 regulates lymphocyte-mediated secretion and cytotoxicity.

Munc18b/STXBP2 is required for platelet secretion.

Platelets are vital for hemostasis because they release their granule contents in response to vascular damage. Platelet exocytosis is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), whose interactions are governed by regulators, eg, Sec/Munc18 proteins. These proteins chaperone syntaxin t-SNAREs and are required for exocytosis. Platelets contain 3 Mu...

Analysis of Familial Hemophagocytic Lymphohistiocytosis Type 4 (FHL-4) Mutant Proteins Reveals that S-Acylation Is Required for the Function of Syntaxin 11 in Natural Killer Cells

Natural killer (NK) cell secretory lysosome exocytosis and cytotoxicity are impaired in familial hemophagocytic lymphohistiocytosis type 4 (FHL-4), a disorder caused by mutations in the gene encoding the SNARE protein syntaxin 11. We show that syntaxin 11 binds to SNAP23 in NK cells and that this interaction is reduced by FHL-4 truncation and frameshift mutation proteins that delete all or part...

Molecular Mechanisms Regulating Cytotoxic Lymphocyte Development and Function, and Their Associations to Human Diseases

Cytotoxic lymphocytes, encompassing cytotoxic T cells and natural killer (NK) cells, play a pivotal role in immune defense. By directed release of perforin-containing lytic granules, cytotoxic lymphocytes can eradicate pathogen-infected, tumorigenic, and otherwise stressed cells. By the virtue of cytokine and chemokine secretion, they can also influence other cells of the immune system. In addi...

VAMP8-dependent fusion of recycling endosomes with the plasma membrane facilitates T lymphocyte cytotoxicity

Cytotoxic T lymphocytes (CTLs) eliminate infected and neoplastic cells through directed release of cytotoxic granule contents. Although multiple SNARE proteins have been implicated in cytotoxic granule exocytosis, the role of vesicular SNARE proteins, i.e., vesicle-associated membrane proteins (VAMPs), remains enigmatic. VAMP8 was posited to represent the cytotoxic granule vesicular SNARE prote...

Cutting Edge: Tyk2 Is Required for the Induction and Nuclear Translocation of Daxx Which Regulates IFN- -Induced Suppression of B Lymphocyte Formation