Syntaxin 11 binds Vti1b and regulates late endosome to lysosome fusion in macrophages
Offenhauser, Carolin , Lei, Nazi , Roy, Sandrine , Collins, Brett , Stow, Jennifer , & Murray, Rachael (2011) Syntaxin 11 binds Vti1b and regulates late endosome to lysosome fusion in macrophages. Traffic (Malden) : the international journal of intracellular transport, 12(6), pp. 762-773.
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 endosomalmembranes 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 arerescued 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.
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|Item Type:||Journal Article|
|Keywords:||FHL-4, late endosomes, lysosomes, SNARE, syntaxin 11|
|Subjects:||Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Protein Trafficking (060108)|
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > IMMUNOLOGY (110700) > Immunology not elsewhere classified (110799)
|Divisions:||Current > Schools > School of Biomedical Sciences|
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2011 Wiley-Blackwell Publishing|
|Deposited On:||15 May 2012 12:44|
|Last Modified:||15 May 2012 12:45|
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