Disease relevance of STX7

• Screening of a large number of tissues and cell lines revealed that Syntaxin 7 is expressed at very high levels in B16 melanoma cells [1].
• Involvement of syntaxin 7 in human gastric epithelial cell vacuolation induced by the Helicobacter pylori-produced cytotoxin VacA [2].
• Analysis in two independent melanoma cohorts demonstrated STX7 expression in nearly all investigated tumors, although at varying levels (> 90% positive tumors) [3].

High impact information on STX7

• Immunocytochemistry revealed that endogenous syntaxin 7 was localized to vacuoles induced by VacA [2].
• Transient transfection of dominant-negative mutant syntaxin 7, which lacks a carboxyl-terminal transmembrane domain, inhibited VacA-induced vacuolation [2].
• Only syntaxin 7 adopts a closed conformation, whereas in vti1b and syntaxin 8, the N-terminal domains do not interact with the adjacent SNARE motifs [4].
• These studies indicate that: 1) fusion along the endocytic pathway is a highly regulated process, and 2) two SNARE molecules, Syntaxin 7 and human VAMP-7, are involved in fusion of vesicles in the late endocytic pathway in alveolar macrophages [5].
• Using homogenous populations of endosomes, we have identified Syntaxin 7 as a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) required for late endosome-lysosome and homotypic lysosome fusion in vitro [5].

Biological context of STX7

• Syntaxin 7 is mainly localized to vacuolar early endosomes (EEs) and may be involved in protein trafficking from the plasma membrane to the EE as well as in homotypic fusion of endocytic organelles [6].
• Accordingly, the rate of SNARE complex assembly is retarded about 7-fold when syntaxin 7 contains its N-terminal domain, whereas the N-terminal domains of vti1b and syntaxin 8 have no influence on assembly kinetics [4].
• The syntaxin 7 gene is localized to human chromosome 6 [7].
• We now report the identification of syntaxin 7 from a human brain cDNA library [7].
• It requires syntaxin 7 as part of the functional trans-SNARE [SNAP receptor, where SNAP is soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein] complex and the release of lumenal calcium to achieve membrane fusion [8].

Anatomical context of STX7

• Syntaxin 7 is a SNARE (soluble N -ethylmaleimide-sensitive fusion protein attachment protein receptor) protein that is present and active in D. discoideum endosomes [Bogdanovic, Bruckert, Morio and Satre (2000) J. Biol. Chem. 275, 36691-36697] [9].
• A bacterially expressed human Syntaxin 7 lacking the transmembrane domain inhibited homotypic late endosome and lysosome fusion as well as heterotypic late endosome-lysosome fusion [5].
• In vitro binding studies reveal that syntaxin 7 binds alphaSNAP, a key regulator of transport vesicle fusion at multiple stages of the secretory pathway [7].
• Based on its homology to yeast and plant vacuolar syntaxins, we propose that syntaxin 7 has a role in vesicle trafficking between the Golgi complex and lysosomes [7].
• Syntaxin 7 was not expressed in undifferentiated HL-60 cells, but its expression was induced on neutrophil differentiation [10].

Physical interactions of STX7

• We first showed that Dictyostelium syntaxin 7 was able to form a complex with N-ethylmaleimide-sensitive fusion protein and alpha- and gamma-soluble N-ethylmaleimide-sensitive fusion protein attachment protein [11].

Other interactions of STX7

• Differential roles of syntaxin 7 and syntaxin 8 in endosomal trafficking [6].
• Overexpression of the myc-tagged protein resulted in an anomalous staining pattern of SNARE molecules participating in ER-Golgi transport such as syntaxin 5 and mammalian bet1, but not the endosomal SNARE syntaxin 7 [12].

Analytical, diagnostic and therapeutic context of STX7

• From a large scale Syntaxin 7 immunoprecipitation, we have identified six polypeptides using a combination of electrospray mass spectrometry and immunoblotting [1].
• Northern and Western blotting demonstrated that VacA intoxication increased syntaxin 7 mRNA and protein expression, respectively, in a time-dependent manner [2].
• Immunoprecipitation and gel filtration studies showed that the mammalian Class C Vps proteins constitute a large hetero-oligomeric complex that interacts with syntaxin-7 [13].

References