Shiga toxin type-2 (Stx2) induces glutamate release via phosphoinositide 3-kinase (PI3K) pathway in murine neurons.
Shiga toxin-producing Escherichia coli (STEC) can cause central nervous system (CNS) damage resulting in paralysis, seizures, and coma. The key STEC virulence factors associated with systemic illness resulting in CNS impairment are Shiga toxins (Stx). While neurons express the Stx receptor globotri...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-07-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnmol.2015.00030/full |
| _version_ | 1828237407808389120 |
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| author | Fumiko eObata Fumiko eObata Lauren M Hippler Progyaparamita eSaha Dakshina M Jandhyala Olga eLatinovic Olga eLatinovic |
| author_facet | Fumiko eObata Fumiko eObata Lauren M Hippler Progyaparamita eSaha Dakshina M Jandhyala Olga eLatinovic Olga eLatinovic |
| author_sort | Fumiko eObata |
| collection | DOAJ |
| description | Shiga toxin-producing Escherichia coli (STEC) can cause central nervous system (CNS) damage resulting in paralysis, seizures, and coma. The key STEC virulence factors associated with systemic illness resulting in CNS impairment are Shiga toxins (Stx). While neurons express the Stx receptor globotriaosylceramide (Gb3) in vivo, direct toxicity to neurons by Stx has not been studied. We used murine neonatal neuron cultures to study the interaction of Shiga toxin type 2 (Stx2) with cell surface expressed Gb3. Single molecule imaging three dimensional STochastic Optical Reconstruction Microscopy - Total Internal Reflection Fluorescence (3D STORM-TIRF) allowed visualization and quantification of Stx2-Gb3 interactions. Furthermore, we demonstrate that Stx2 increases neuronal cytosolic Ca2+, and NMDA-receptor inhibition blocks Stx2-induced Ca2+ influx, suggesting that Stx2-mediates glutamate release. Phosphoinositide 3-kinase (PI3K)-specific inhibition by Wortmannin reduces Stx2-induced intracellular Ca2+ indicating that the PI3K signaling pathway may be involved in Stx2-associated glutamate release, and that these pathways may contribute to CNS impairment associated with STEC infection. |
| first_indexed | 2024-04-12T20:47:04Z |
| format | Article |
| id | doaj.art-7578da6768a0429f9bd820939d7ac129 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-12T20:47:04Z |
| publishDate | 2015-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-7578da6768a0429f9bd820939d7ac1292022-12-22T03:17:14ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992015-07-01810.3389/fnmol.2015.00030148213Shiga toxin type-2 (Stx2) induces glutamate release via phosphoinositide 3-kinase (PI3K) pathway in murine neurons.Fumiko eObata0Fumiko eObata1Lauren M Hippler2Progyaparamita eSaha3Dakshina M Jandhyala4Olga eLatinovic5Olga eLatinovic6University of YamanashiUniversity of Maryland School of MedicineUniversity of Maryland School of MedicineUniversity of Maryland School of MedicineTufts UniversityUniversity of Maryland School of MedicineUniversity of Maryland School of MedicineShiga toxin-producing Escherichia coli (STEC) can cause central nervous system (CNS) damage resulting in paralysis, seizures, and coma. The key STEC virulence factors associated with systemic illness resulting in CNS impairment are Shiga toxins (Stx). While neurons express the Stx receptor globotriaosylceramide (Gb3) in vivo, direct toxicity to neurons by Stx has not been studied. We used murine neonatal neuron cultures to study the interaction of Shiga toxin type 2 (Stx2) with cell surface expressed Gb3. Single molecule imaging three dimensional STochastic Optical Reconstruction Microscopy - Total Internal Reflection Fluorescence (3D STORM-TIRF) allowed visualization and quantification of Stx2-Gb3 interactions. Furthermore, we demonstrate that Stx2 increases neuronal cytosolic Ca2+, and NMDA-receptor inhibition blocks Stx2-induced Ca2+ influx, suggesting that Stx2-mediates glutamate release. Phosphoinositide 3-kinase (PI3K)-specific inhibition by Wortmannin reduces Stx2-induced intracellular Ca2+ indicating that the PI3K signaling pathway may be involved in Stx2-associated glutamate release, and that these pathways may contribute to CNS impairment associated with STEC infection.http://journal.frontiersin.org/Journal/10.3389/fnmol.2015.00030/fullEscherichia coliGlutamatesNeuronsShiga Toxin 2super resolution microscopyPI3K pathway |
| spellingShingle | Fumiko eObata Fumiko eObata Lauren M Hippler Progyaparamita eSaha Dakshina M Jandhyala Olga eLatinovic Olga eLatinovic Shiga toxin type-2 (Stx2) induces glutamate release via phosphoinositide 3-kinase (PI3K) pathway in murine neurons. Frontiers in Molecular Neuroscience Escherichia coli Glutamates Neurons Shiga Toxin 2 super resolution microscopy PI3K pathway |
| title | Shiga toxin type-2 (Stx2) induces glutamate release via phosphoinositide 3-kinase (PI3K) pathway in murine neurons. |
| title_full | Shiga toxin type-2 (Stx2) induces glutamate release via phosphoinositide 3-kinase (PI3K) pathway in murine neurons. |
| title_fullStr | Shiga toxin type-2 (Stx2) induces glutamate release via phosphoinositide 3-kinase (PI3K) pathway in murine neurons. |
| title_full_unstemmed | Shiga toxin type-2 (Stx2) induces glutamate release via phosphoinositide 3-kinase (PI3K) pathway in murine neurons. |
| title_short | Shiga toxin type-2 (Stx2) induces glutamate release via phosphoinositide 3-kinase (PI3K) pathway in murine neurons. |
| title_sort | shiga toxin type 2 stx2 induces glutamate release via phosphoinositide 3 kinase pi3k pathway in murine neurons |
| topic | Escherichia coli Glutamates Neurons Shiga Toxin 2 super resolution microscopy PI3K pathway |
| url | http://journal.frontiersin.org/Journal/10.3389/fnmol.2015.00030/full |
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