Disease relevance of STX6

• In addition, syntaxin 6 inhibition decreased the delivery of GM1 ganglioside (GM1) and glycosylphosphatidylinositol (GPI)-GFP (but not vesicular stomatitis virus-glycoprotein G; VSV-G) protein from the Golgi complex to the plasma membrane [1].

High impact information on STX6

• Syntaxin 6 inhibition also reduced the presence of caveolin-1 and caveolae at the plasma membrane [1].
• Regulation of caveolar endocytosis by syntaxin 6-dependent delivery of membrane components to the cell surface [1].
• When syntaxin 6 function was inhibited, internalization through caveolae was dramatically reduced, whereas other endocytic mechanisms were unaffected [1].
• Addition of GM1 to syntaxin 6-inhibited cells resulted in the reappearance of caveolin-1 and caveolae at the plasma membrane, and restored caveolar uptake [1].
• Here, we demonstrate that caveolar endocytosis is regulated by syntaxin 6, a target membrane soluble N-ethylmaleimide attachment protein receptor (t-SNARE) involved in membrane fusion events along the secretory pathway [1].

Biological context of STX6

• Involvement of SNAP-23 and syntaxin 6 in human neutrophil exocytosis [2].
• The binding site for syntaxin-6 overlaps with that of Rab5-GTP at the C terminus of EEA1 [3].
• The sequence homology, topology, localization, and alpha-SNAP binding suggest that syntaxin 6 is involved in intracellular vesicle trafficking [4].
• The induced phosphorylation of syntaxin 6 was not effectively blocked by either Rp-8-Br-PET-cGMP or LY294002 [5].
• Using a series of GST fusion protein binding assays, co-immunofluorescence and co-immunoprecipitation experiments, we show that FIG specifically binds to the coiled coil domain-containing Q-SNARE (Q-soluble NSF attachment protein receptor) protein syntaxin 6 both in vitro and in vivo [6].

Anatomical context of STX6

• SNAP-23 was translocated to the cell surface, colocalizing with syntaxin 6, on neutrophil activation [2].
• Syntaxin 6 was localized mainly in the plasma membrane of human resting neutrophils, whereas SNAP-23 was located primarily in the mobilizable tertiary and specific granules [2].
• Here we demonstrate that EEA1 interacts directly and specifically with syntaxin-6, a SNARE implicated in trans-Golgi network to early endosome trafficking [3].
• Syntaxin-6 and EEA1 were found to colocalize extensively on early endosomes, although syntaxin-6 is present in the trans-Golgi network as well [3].
• Results: Vesicle-associated membrane proteins-7 and -8 were localized to granule and membrane-enriched fractions in eosinophils and neutrophils, whereas syntaxin-6 was not detectable [7].

Associations of STX6 with chemical compounds

• PTP-MEG2 reduced the phosphotyrosine content of NSF and co-localized with NSF and syntaxin 6 in intact cells [8].
• Brefeldin A treatment clearly shows that the observed perinuclear localization of syndapin II co-localizing with syntaxin 6 reflects the Golgi complex and that it requires functional integrity of the Golgi [9].
• We found that STX6 is necessary for proper expression of focal adhesion kinase and integrin alpha5 adhesion receptor [10].

Physical interactions of STX6

• Immunoprecipitation of VAMP4 from rat brain detergent extracts revealed that VAMP4 exists in a complex containing syntaxin 6 [11].
• In vitro binding studies established that SNAP-23 binds to syntaxin 6 [2].
• Moreover, Syt IV CD binds specifically to ISGs and not to mature secretory granules (MSGs), and Syt IV binds to syntaxin 6, a SNARE protein that is involved in ISG maturation [12].

Co-localisations of STX6

• In these compartments, VAMP4 was found to colocalize with the putative TGN-trafficking protein syntaxin 6 [11].

Other interactions of STX6

• The maturation block involves interference with the recruitment and function of rabs, rab effectors (phosphatidylinositol 3-kinases and tethering molecules such as EEA1), SNAREs (Syntaxin 6 and cellubrevin) and Ca2+/calmodulin signaling [13].
• Syntaxin-4, but not syntaxin-6, was found to interact with SNAP-23 and was partially involved in mediator secretion from multiple compartments [7].
• We demonstrate that fusion is largely mediated by a complex formed by syntaxin 13, syntaxin 6, vti1a, and VAMP4, whereas the exocytic and late endosomal SNAREs play little or no role in the reaction [14].
• Syntaxin 16 knockdown with small interfering RNA (siRNA) affects the TGN localization of syntaxin 6 but not syntaxin 10, and clearly inhibits endosome-TGN transport [15].
• On the other hand, knockdown of syntaxin 10 expressions had no significant effect on the TGN localization of syntaxin 6 and 16, and did not inhibit endosome-TGN transport [15].

Analytical, diagnostic and therapeutic context of STX6

• This notion is confirmed using magnetic immunoisolation of PS1- or syntaxin 6-positive membrane patches from a mixture of membranes with similar buoyant densities following Lubrol WX extraction or sonication, and gradient centrifugation [16].

References