Disease relevance of Stx1a

• In the current study, we overexpressed syntaxin 1A, SNAP-25b, and VAMP-2 in PC12 cells using recombinant adenoviruses, and determined their effects on membrane trafficking involving neurite outgrowth [1].
• The STX-1A mice displayed fasting hyperglycemia and a more sustained elevation of plasma glucose levels after an intraperitoneal glucose tolerance test, with correspondingly reduced plasma insulin levels [2].
• The differentiation states of neurons in primary cultures were determined by the sensitivity of neurons to glutamate toxicity and the expression of specific proteins such as the phosphorylated form of a 200-kDa neurofilament, HPC-1/syntaxin 1A, and cell adhesion molecule L1 [3].
• Overexpressed syntaxin 1A/HPC-1 inhibits insulin secretion via a regulated pathway, but does not influence glucose metabolism and intracellular Ca2+ in insulinoma cell line beta TC3 cells [4].

High impact information on Stx1a

• However, this organelle did not contain SV2, another synaptic vesicle protein, nor did it contain presynaptic membrane proteins, such as syntaxin 1A or SNAP-25, or other known anterograde motor proteins, such as kinesin and KIF3 [5].
• Thus, granuphilin not only is essential for the docking of insulin granules but simultaneously imposes a fusion constraint on them through an interaction with the syntaxin-1a fusion machinery [6].
• Here we demonstrate that granuphilin directly binds to syntaxin 1a on the plasma membrane, and this interaction is regulated by Rab27a [7].
• Granuphilin modulates the exocytosis of secretory granules through interaction with syntaxin 1a [7].
• Here we have analyzed the trafficking of syntaxin 1A in INS-1 and CHO cells [8].

Biological context of Stx1a

• The effect of syntaxin 1A in general membrane trafficking was further studied by transient transfection of non-neuronal cells [1].
• Syntaxin 1A binds the NH(2) terminal domain of NET, and a deletion of this domain both eliminates NET/syntaxin 1A associations and prevents phorbol ester-triggered NET downregulation [9].
• SNAP25 endosomes, which exclude the plasma membrane SNARE syntaxin 1A, merge with those derived from clathrin-dependent endocytosis containing endosomal syntaxin 13 [10].
• Furthermore, we investigated the phosphorylation of HPC-1/syntaxin 1A in the rat brain membranes [11].
• Islet levels of STX-1A and cognate SNARE proteins are reduced in type 2 diabetic rodents, suggesting their role in dysregulated insulin secretion contributing to the abnormal glucose homeostasis [2].

Anatomical context of Stx1a

• The protein HPC-1/syntaxin 1A is abundantly expressed in neurons and localized in the neuronal plasma membrane [12].
• Participation of syntaxin 1A in membrane trafficking involving neurite elongation and membrane expansion [1].
• Syntaxin 1A has been implicated to play an important role in neurotransmitter release by regulating synaptic vesicle fusion [1].
• It was found that overexpression of syntaxin 1A inhibited NGF-induced neurite extension, and the expressed syntaxin was localized to the plasma membrane, intracellular membranes, and the neurite tips [1].
• Expression of Munc13-1, along with its cognate partners, syntaxin 1a and Munc18a, is reduced in the pancreatic islets of type-2 diabetes non-obese Goto-Kakizaki and obese Zucker fa/fa rats [13].

Associations of Stx1a with chemical compounds

• Overexpression of t-SNAREs, syntaxin 1A, and SNAP-25 inhibited the mastoparan-induced insulin release by approximately half-fold of control levels, however, the mastoparan-induced GABA release was not affected by these t-SNAREs overexpression [14].
• HPC-1/syntaxin 1A affinity-purified on a 14D8 IgG-coupled column was recognized by antiphosphoserine antibody, but not by antiphosphotyrosine and phosphothreonine antibodies [11].

Physical interactions of Stx1a

• Interestingly, we found that SNARE motif-exposed syntaxin 1A mutants were retained in endoplasmic reticulum (ER) and failed to transport to the cell surface in the absence of SNAP-25, suggesting that the exposure of the SNARE motif causes ER retention and complexation with SNAP-25 helps the ER escape [8].

Regulatory relationships of Stx1a

• Rab27 effector granuphilin promotes the plasma membrane targeting of insulin granules via interaction with syntaxin 1a [15].

Other interactions of Stx1a

• The peripheral location of granules is well overlapped with both localizations of granuphilin and syntaxin 1a [15].
• No difference in the morphology, neuritic outgrowth or distribution of SNAP-25, syntaxin 1A, or synaptophysin could be observed in ScGT1-1 cells [16].
• As such, regulation of the interaction between Munc18a and syntaxin 1a may provide an important mechanism controlling secretory responsiveness [17].
• In the current study, we used quantitative in situ hybridisation to examine mRNA expression of SNAREs (25 kDa synaptosome-associated protein (SNAP-25), syntaxin-1A and synaptobrevin-2) and SNARE-associated proteins (alpha-SNAP, CPLXI and CPLXII) in brain of R6/2 mice and their wild type littermates between 3 and 15 weeks of age [18].
• Syntaxin-3 and syntaxin-1A inhibit L-type calcium channel activity, insulin biosynthesis and exocytosis in beta-cell lines [19].

References