Caspase-11 and caspase-1 differentially modulate actin polymerization via RhoA and Slingshot proteins to promote bacterial clearance
| Autor: | Kyle Caution, Mikhail A. Gavrilin, Daniel Layman, Mia Tazi, Kathrin Krause, Amal O. Amer, Sheshadri Hoque, Apurva Kanneganti |
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| Rok vydání: | 2015 |
| Předmět: |
Cofilin 1
0301 basic medicine RHOA Inflammasomes Vesicular Transport Proteins Receptors Cell Surface macromolecular substances Caspase-11 Vacuole Article Legionella pneumophila Mice 03 medical and health sciences Phosphoprotein Phosphatases medicine Animals Humans Actin Mice Knockout Multidisciplinary Slingshot biology Caspase 1 Inflammasome Cofilin Actins Cell biology 030104 developmental biology Multiprotein Complexes Vacuoles biology.protein Legionnaires' Disease Lysosomes rhoA GTP-Binding Protein medicine.drug |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Inflammasomes are multiprotein complexes that include members of the NOD-like receptor family and caspase-1. Caspase-1 is required for the fusion of the Legionella vacuole with lysosomes. Caspase-11, independently of the inflammasome, also promotes phagolysosomal fusion. However, it is unclear how these proteases alter intracellular trafficking. Here, we show that caspase-11 and caspase-1 function in opposing manners to phosphorylate and dephosphorylate cofilin, respectively upon infection with Legionella. Caspase-11 targets cofilin via the RhoA GTPase, whereas caspase-1 engages the Slingshot phosphatase. The absence of either caspase-11 or caspase-1 maintains actin in the polymerized or depolymerized form, respectively and averts the fusion of pathogen-containing vacuoles with lysosomes. Therefore, caspase-11 and caspase-1 converge on the actin machinery with opposing effects to promote vesicular trafficking. |
| Databáze: | OpenAIRE |
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