High impact information on STX3

• Cholesterol depletion causes dispersion of syntaxin 3 but not syntaxin 4 clusters [1].
• Syntaxin 3 and 4 cluster formation depends on different mechanisms because the integrity of syntaxin 3 clusters depends on intact microtubules, whereas syntaxin 4 clusters depend on intact actin filaments [1].
• Small interfering RNA-induced knockdown of syntaxin 4 (but not of syntaxin 3) inhibited exocytosis of WPBs as detected by the reduction in thrombin-induced cell surface P-selectin expression [2].
• In polarized epithelial cells syntaxin 3 is at the apical plasma membrane and is involved in delivery of proteins from the trans-Golgi network to the apical surface [3].
• We identified the presence of syntaxin 4, syntaxin 3, and the high affinity syntaxin 4-regulatory protein Munc18c in human lung microvascular endothelial cells [2].

Biological context of STX3

• We suggest that TI-VAMP, SNAP23, and syntaxin 3 can participate in exocytotic processes at the apical plasma membrane of epithelial cells and, more generally, domain-specific exocytosis in clostridial NT-resistant pathways [4].
• This apical localization was confirmed by confocal microscopy after transfection of the cDNA coding for either full length or N-terminally truncated human syntaxin 3 in Caco-2 cells [5].
• Functionally, co-expression of BKCa channels with syntaxin 1A, but not syntaxin 3, was observed to enhance channel gating and kinetics at low concentrations (1-4 microM) of free cytosolic calcium, but not at higher concentrations (< or = 10 microM), as judged by macroscopic current recordings in excised membrane patches [6].
• RESULTS: We have identified and purified a novel binding partner of syntaxin-3 from rat lung, and isolated and sequenced the cDNA of its human homologue from a human brain cDNA library [7].
• Introduction of a point mutation into syntaxin 3 abolishes its polarized distribution and causes PSMA to be targeted in a nonpolarized fashion [8].

Anatomical context of STX3

• Here we show that syntaxin 3 (STX3), a plasma membrane protein, has an important role in the growth of neurites, and also serves as a direct target for omega-6 arachidonic acid [9].
• Munc18-2, a functional partner of syntaxin 3, controls apical membrane trafficking in epithelial cells [10].
• We demonstrate here that Munc-18-2 colocalizes with syntaxin 3 at the apical plasma membrane of intestinal epithelium and Caco-2 cells [11].
• STX3 was therefore cloned by single-cell sorting, and a panel of 102 splenic stromal cell lines was established [12].
• The STX3 stroma is an immortalised mixed population of endothelial cells and elongated spindle-shaped cells, thought to be fibroblasts [13].

Associations of STX3 with chemical compounds

• The quantity of the complex is reduced by treatment of Caco-2 cells with the alkylating agent N-ethylmaleimide which also has an inhibitory effect on the ability of Munc-18-2 to associate with syntaxin 3 in vitro [11].

Physical interactions of STX3

• Immunoprecipitation experiments revealed a direct association of syntaxin 13 and full-length ABCA1, whereas syntaxin 3 and 6 failed to interact with ABCA1 [14].

Regulatory relationships of STX3

• Basal ENaC currents were inhibited by syntaxin 1A and stimulated by syntaxin 3 [15].

Other interactions of STX3

• This implies that Munc18-2 function in apical membrane trafficking involves aspects independent of the syntaxin 3 interaction [10].
• This suggests that, although syntaxin 3 is the main target SNARE operating in exocytic transport to the apical plasma membrane in certain epithelial cell types, syntaxin 2 may play an important role in this trafficking route in others [16].
• This inhibitory effect is selective for S1A and is not reproduced by syntaxin 3 [17].
• In contrast, transient transfection with either dominant-negative mutant syntaxin 3 or 7 did not affect MT1-MMP localization on the plasma membrane [18].
• Cloning of STX3 led to the isolation of a panel of splenic endothelial cell lines heterogeneous in terms of morphology and hematopoietic support function [13].

Analytical, diagnostic and therapeutic context of STX3

• Dissection of cellular components of the STX3 stroma should provide information about a niche for DC development [12].
• Using a reciprocal co-immunoprecipitation strategy, we observed that native BKCa channels in rat hippocampus co-associate with syntaxin 1A, but not the closely related homologue syntaxin 3 [6].
• Western blotting showed that syntaxin 3 and 4 proteins, which are known to function in intracellular transport towards the plasma membrane, were expressed in AGS cells [18].

References