Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is required for autophagosome maturation
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UMass Chan AffiliationsDepartment of Neurology
Document TypeJournal Article
Endosomal Sorting Complexes Required for Transport
Vesicular Transport Proteins
Cell and Developmental Biology
Cellular and Molecular Physiology
Genetics and Genomics
Neuroscience and Neurobiology
MetadataShow full item record
AbstractPhagophore maturation is a key step in the macroautophagy pathway, which is critical in many important physiological and pathological processes. Here we identified Drosophila N-ethylmaleimide-sensitive fusion protein 2 (dNSF2) and soluble NSF attachment protein (Snap) as strong genetic modifiers of mutant CHMP2B, an ESCRT-III component that causes frontotemporal dementia and autophagosome accumulation. Among several SNAP receptor (SNARE) genes, Drosophila syntaxin 13 (syx13) exhibited a strong genetic interaction with mutant CHMP2B. Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a in mammalian cells caused LC3-positive puncta to accumulate and blocks autophagic flux. STX13 was present on LC3-positive phagophores induced by rapamycin and was highly enriched on multilamellar structures induced by dysfunctional ESCRT-III. Loss of STX13 also caused the accumulation of Atg5-positive puncta and the formation of multilamellar structures. These results suggest that STX13 is a genetic modifier of ESCRT-III dysfunction and participates in the maturation of phagophores into closed autophagosomes.
SourceMol Cell. 2013 Oct 24;52(2):264-71. doi: 10.1016/j.molcel.2013.08.041. Epub 2013 Oct 3. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/30498
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