Syntaxin 11 binds Vti1b and regulates late endosome to lysosome fusion in macrophages

Offenhäuser, Carolin, Lei, Nazi, Roy, Sandrine, Collins, Brett M., Stow, Jennifer L. and Murray, Rachael Z. (2011) Syntaxin 11 binds Vti1b and regulates late endosome to lysosome fusion in macrophages. Traffic, 12 6: 762-773. doi:10.1111/j.1600-0854.2011.01189.x

Author Offenhäuser, Carolin
Lei, Nazi
Roy, Sandrine
Collins, Brett M.
Stow, Jennifer L.
Murray, Rachael Z.
Title Syntaxin 11 binds Vti1b and regulates late endosome to lysosome fusion in macrophages
Journal name Traffic   Check publisher's open access policy
ISSN 1398-9219
Publication date 2011-06-01
Sub-type Article (original research)
DOI 10.1111/j.1600-0854.2011.01189.x
Volume 12
Issue 6
Start page 762
End page 773
Total pages 12
Place of publication Malden, MA, U.S.A.
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Syntaxin 11 (Stx11) is a SNARE protein enriched in cells of the immune system. Loss or mutation of Stx11 results in familial hemophagocytic lymphohistiocytosis type-4 (FHL-4), an autosomal recessive disorder of immune dysregulation characterized by high levels of inflammatory cytokines along with defects in T-cell and natural killer cell function. We show here Stx11 is located on endosomal membranes including late endosomes and lysosomes in macrophages. While Stx11 did not form a typical trans-SNARE complex, it did bind to the Q-SNARE Vti1b and was able to regulate the availability of Vti1b to form the Q-SNARE complexes Stx6/Stx7/Vtib and Stx7/Stx8/Vti1b. The mutant form of Stx11 sequestered Vti1b from forming the Q-SNARE complex that mediates late endosome to lysosome fusion. Depletion of Stx11 in activated macrophages leads to an accumulation of enlarged late endocytic compartments, increased trafficking to the cell surface and inhibition of late endosome to lysosome fusion. These phenotypes are rescued by the expression of an siRNA-resistant Stx11 construct in Stx11-depleted cells. Our results suggest that by regulating the availability of Vti1b, Stx11 regulates trafficking steps between late endosomes, lysosomes and the cell surface in macrophages.
Keyword FHL-4
Late endosomes
Syntaxin 11
SNARE complex
Hemophagocytic lymphohistiocytosis
Cytokine secretion
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 31 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 32 times in Scopus Article | Citations
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Created: Tue, 20 Sep 2011, 22:15:28 EST by Brett Collins on behalf of Institute for Molecular Bioscience