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Voltage-dependent c...
Voltage-dependent calcium channel signaling mediates GABA(A) receptor-induced migratory activation of dendritic cells infected by Toxoplasma gondii
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- Kanatani, Sachie (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Fuks, Jonas M. (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Olafsson, Einar B. (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Westermark, Linda (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Chambers, Benedict (author)
- Karolinska Institutet
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- Varas-Godoy, Manuel (author)
- Karolinska Institutet
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- Uhlén, Per (author)
- Karolinska Institutet
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- Barragan, Antonio (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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(creator_code:org_t)
- 2017-12-07
- 2017
- English.
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In: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 13:12
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Abstract
Subject headings
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- The obligate intracellular parasite Toxoplasma gondii exploits cells of the immune system to disseminate. Upon T. gondii-infection,. Upsilon-aminobutyric acid (GABA)/GABAA receptor signaling triggers a hypermigratory phenotype in dendritic cells (DCs) by unknown signal transduction pathways. Here, we demonstrate that calcium (Ca2+) signaling in DCs is indispensable for T. gondii-induced DC hypermotility and transmigration in vitro. We report that activation of GABAA receptors by GABA induces transient Ca2+ entry in DCs. Murine bone marrow-derived DCs preferentially expressed the L-type voltage-dependent Ca2+ channel (VDCC) subtype Cav1.3. Silencing of Cav1.3 by short hairpin RNA or selective pharmacological antagonism of VDCCs abolished the Toxoplasma-induced hypermigratory phenotype. In a mouse model of toxoplasmosis, VDCC inhibition of adoptively transferred Toxoplasma-infected DCs delayed the appearance of cell-associated parasites in the blood circulation and reduced parasite dissemination to target organs. The present data establish that T. gondii-induced hypermigration of DCs requires signaling via VDCCs and that Ca2+ acts as a second messenger to GABAergic signaling via the VDCC Cav1.3. The findings define a novel motility-related signaling axis in DCs and unveil that interneurons and DCs share common GABAergic motogenic pathways. T. gondii employs GABAergic non-canonical pathways to induce host cell migration and facilitate dissemination.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Keyword
- molekylär biovetenskap
- Molecular Bioscience
Publication and Content Type
- ref (subject category)
- art (subject category)
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