We describe a novel syntaxin family member, syntaxin 9 (Syn 9), which does not possess a typical C-terminal hydrophobic tail anchor. Syn 9 has, however, a Q-SNARE domain and an overall homology to syntaxins (with the highest overall homology with mammalian syntaxin 11). Syn 9 is enriched in some epithelial cells, particularly that of the stomach lining and the skin. At the skin, it is found in the epidermal layers as well as structures associated with hair follicles. A biochemical interaction screen revealed that Syn 9 interacts specifically with the epidermal growth factor (EGF) receptor. Overexpression of Syn 9 perturbed EGF receptor endocytosis but does not appear to affect the internalization of the transferrin receptor. Syn 9 may therefore have a role in EGF receptor transport and signaling in certain epithelial cell types. Membrane transport along the exocytic and endocytic pathways is mediated by evolutionarily conserved molecular machineries. Fusion and the specificity of fusion of transport vesicles to target membrane are mediated by soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors (SNAREs) (1-3). All SNAREs are characterized by the presence of one or more signature motif known as the SNARE domain (4), which participates directly in the formation of SNARE complexes. They can be structurally subdivided into three subfamilies -VAMPs, syntaxins, and the SNAP25 family. Alternatively, SNAREs have been broadly divided into either vesicle (v)-SNAREs (if found on vesicles) or target (t)-SNAREs (if found on target membranes), and more recently into Q-or R-SNAREs based on the presence of either a critical glutamine or arginine residue within a particular position in the SNARE domain (5).SNARE proteins have been initially identified (and still best characterized) as molecules involved in mediating synaptic vesicle docking and fusion. The prototype member of one of its subfamilies, the syntaxins, is the neuronal SNARE syntaxin 1A. Syntaxin 1A was first characterized based on its involvement in the regulation of neurotransmitter release (6). Its localization on the presynaptic plasma membrane makes it a target (t)-SNARE. Fifteen syntaxins in the human genome have since been identified and characterized to date (7-21). These are localized at different subcellular compartments and mediate membrane fusion events in both the exocytic and endocytic pathways. All syntaxins identified to date are type II-like polypeptides with a C-terminal hydrophobic membranespanning anchor, with the exception of syntaxin 11 (16,17). We describe in this report a novel syntaxin molecule, which we call syntaxin 9 (Syn 9) which is also without a C-terminal transmembrane anchor. We found that Syn 9 is enriched in the epithelial cells of some tissues and may have a role in epidermal growth factor (EGF) receptor trafficking or signaling in these cells. ResultsIn silico identification of Syn 9 Database searches had revealed an entry of mouse cDNA (BC023414) with homology to syntaxins. An expressed sequence tag ...
Ricin is a toxin that can be easily extracted from seeds of Ricinus communis plants. Ricin is considered to be a major bio-threat as it can be freely and easily acquired in large quantities. A deliberate release of such toxin in civilian populations would very likely overwhelm existing public health systems, resulting in public fear and social unrest. There is currently no commercially available or FDA-approved prophylaxis such as vaccines, or therapeutic antitoxins or antidotes, available for ricin intoxication. Patient treatment is typically supportive care based on symptoms, often designed to reinforce the body's natural response. This paper describes the development and validation of a robust ELISA test kit, which can be used to screen for ricin in biological specimens such as whole blood and faeces. Faecal specimens are shown in this study to have better diagnostic sensitivity and a wider diagnostic window compared to whole blood. From these results, it is concluded that faeces is the most suitable clinical specimen for diagnosis of ricin poisoning via the oral route. The ELISA test kit can also detect ricin in environmental samples. An advantage of this ELISA kit over other commercial off-the-shelf (COTS) detection kits currently on the market that are developed to screen environmental samples only is its ability to diagnose ricin poisoning from clinical specimens as well as detect ricin from environmental samples.
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