Disease relevance of Stx2

• In the pericentral zone, reactivity for epimorphin was markedly enhanced concurrently with appearance of granulomas [1].
• Epimorphin(-/-) mice have increased intestinal growth, decreased susceptibility to dextran sodium sulfate colitis, and impaired spermatogenesis [2].
• Epimorphin overexpression in the mouse mammary gland promotes alveolar hyperplasia and mammary adenocarcinoma [3].
• Shiga toxin 2 (Stx2) is produced by enterohemorrhagic Escherichia coli (EHEC) and is known as the major virulence factor of EHEC [4].
• Shiga toxin type 2 (Stx2) produced by Escherichia coli O:157H7 can cause hemolytic-uremic syndrome in children, a disease for which there is neither a vaccine nor an effective treatment [5].

Psychiatry related information on Stx2

• The aim of this study was to evaluate the effects of Stx2 on (i) maternal lethality, (ii) fetuses, (iii) delivery period, and (iv) maternal behavior after delivery [4].

High impact information on Stx2

• Delivering the message: epimorphin and mammary epithelial morphogenesis [6].
• Here, we outline the fundamentals of mammary gland development and describe the function of epimorphin in these processes [6].
• These in vivo findings support the notion that epimorphin is a key stromal regulator of epithelial cell proliferation and growth in the intestine [2].
• In addition, our studies demonstrate a novel and critical role for epimorphin in regulating testicular development and growth as well as spermatogenesis [2].
• Colonic mucosal injury and colitis induced by dextran sodium sulfate (DSS) are ameliorated in epimorphin-/- mice, probably due to the increased proliferative capacity of the epimorphin-/- colon [2].

Chemical compound and disease context of Stx2

• Re-epithelialization of epimorphin-rich intra-alveolar fibrosis was complete by Day 28 after bleomycin, and by Day 56, epimorphin immunoreactivity had declined [7].

Biological context of Stx2

• Sperm express Syt VI and VIII and Stx2, which are co-localized to the acrosomal compartment where they might mediate exocytosis in response to calcium influx [8].
• Taken together, our data suggest a critical role for Syt VIII and Stx2 in membrane fusion and acrosome reaction in the sperm [8].
• By searching the recent protein data base, it was found that the HPC-1 antigen revealed unusual similarity to epimorphin which was mesenchymal factor related to the morphogenesis of primitive epidermal tissues in embryonic stages [9].
• These results suggest that a certain population of epimorphin molecules is involved in cell/cell interaction through a process of complex formation, transportation to extracellular regions, and direct binding to the cell surface [10].
• Reverse transcription-polymerase chain reaction (RT-PCR) analysis also revealed that epimorphin increased the expression of a trophoblast cell differentiation marker, placental lactogen-1 (PL-1), mRNA (P < 0.01) [11].

Anatomical context of Stx2

• Synaptotagmin VI and VIII and syntaxin 2 are essential for the mouse sperm acrosome reaction [8].
• In unstimulated cells, syntaxin 2 was exclusively present on the apical plasma membrane [12].
• In contrast, after stimulation, syntaxin 2 had moved into the membranes of fused granules, as judged by its location around dye-filled structures of 1-mum diameter that were coated with filamentous actin [12].
• Immunohistochemical analysis confirmed that epimorphin was localized in outgrowing trophoblast cells and ICM [11].
• Treatment with a function inhibitor, rat anti-mouse epimorphin IgM, reduced the number of embryos progressing to blastocyst outgrowth to the levels similar to those observed with plain culture medium [11].

Associations of Stx2 with chemical compounds

• Sodium-dodecyl-sulfate-resistant complex formation of epimorphin monomers and interaction of the 150-kDa complex with the cell surface [10].
• Distribution and isoforms of epimorphin in carbon tetrachloride-induced acute liver injury in mice [1].
• Here, we present the molecular mechanism by which EPM mediates luminal morphogenesis [13].
• Embryonic submandibular gland was used to study the roles of two mesenchymal proteins, epimorphin and tenascin-C, as well as the epithelial protein laminin-1 and one of its integrin receptors on branching morphogenesis [14].
• Co-administration of Stx2 with LPS enhanced and prolonged the KC and MIP-2 host response (RNA and protein) induced by LPS alone [15].

Physical interactions of Stx2

• We found that Stx2 binds to Syt I, VI, and VIII in a calcium-dependent manner with EC(50) values of 175, 233, and 96 mum calcium, respectively [8].
• Slp4-a/granuphilin-a interacts with syntaxin-2/3 in a Munc18-2-dependent manner [16].
• We also show that secreted epimorphin binds to alphav-integrin-containing receptors on target epithelial cells, leading to activation of specific downstream signaling pathways and induction of epithelial morphogenesis [17].

Other interactions of Stx2

• We conclude that syntaxin 2 enters the membrane of a fused zymogen granule after the opening of the fusion pore, and we suggest that this movement might permit the onset of secondary fusion [12].
• It has been suggested that the sequential nature of primary and secondary fusion is a consequence of the requirement for plasma membrane soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors, such as syntaxin 2, to enter the membrane of the primary fused granule [12].
• Deletion analysis showed that the syntaxin-2/3 (or Munc18-1/2)-binding site is a linker domain of Slp4-a (amino acid residues 144-354), a previously uncharacterized region located between the N-terminal Rab27A binding domain and the C2A domain [16].
• Increased expression of epimorphin in bleomycin-induced pulmonary fibrosis in mice [7].
• However, from Day 7 until Day 28 after bleomycin treatment, increasing levels of epimorphin immunoreactivity were detected in the mesenchymal cells and in the extracellular matrix within intra-alveolar fibrotic lesions [7].

Analytical, diagnostic and therapeutic context of Stx2

• Syntaxin 2 was imaged by confocal immunofluorescence microscopy [12].
• In the present study, the expression and potential function of epimorphin in developing conceptuses was investigated through the use of reverse transcription-polymerase chain reaction (RT-PCR), whole mount in situ hybridization/immunohistochemistry, and in vitro blastocyst culture [11].
• However, sequence analysis of the isolated epimorphin cDNA revealed that its product resembled other proteins that are involved in intracellular vesicular transport [10].
• In a previous study using the DNA microarray technique, we had discovered evidence that increase in a transcript for mesenchymal morphogen, epimorphin, was noted as the conceptus attached to the matrix in vitro (Qin et al., 2003) [11].
• The localization of epimorphin in glomerular mesangial cells and interstitial fibroblasts was confirmed by immunoelectron microscopy of 2-week-old mouse kidneys [18].

References