Histiocytic Disorders by Oussama Abla & Gritta Janka

Author:Oussama Abla & Gritta Janka
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

Syntaxin 11 Deficiency Causes FHL4

In patients with FHL4 (MIM 605014), the mean time of HLH onset is later than in patients with FHL2 or FHL3 [36, 37]. FHL4 Patients carry mutations in the syntaxin 11 gene (STX11) [13]. Syntaxin 11 is a member of the t-SNARE family of proteins involved in membrane fusion events. Most of the STX11 mutations reported to date are null mutations and were first identified in patients of Turkish/Kurdish descent, where they account for approximately 20% of FHL cases [38]. Since then, biallelic syntaxin 11 mutations have been identified in patients of different origins. A few missense mutations have also been reported in FHL4 patients, and examination of their functional consequences has helped to identify the syntaxin 11 domain that interacts with the syntaxin-binding protein Munc18-2 [39, 40]. Although the cytotoxic activity of NK cells in FHL4 patients is markedly defective, syntaxin 11-deficient CTLs are less affected and can be partially restored by IL-2 stimulation [41]. The fact that syntaxin 3 expression in cytotoxic lymphocytes can compensate for a lack of functional syntaxin 11, at least in vitro, may account for this functional restoration [39]. Syntaxin 11 is thus yet another effector of the cytotoxic machinery required for the release of cytotoxic granules contents – probably by regulating membrane fusion events [42]. The syntaxin 11-regulated step in the cytotoxic pathway remains to be characterized, although it is probably involved in the fusion between cytotoxic granules and the plasma membrane at the IS (Fig. 11.1).

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