RHOA mediated mechanical force generation through Dectin-1
| Autor: | Tomasz Kołodziej, Alan Buser, Aaron K. Neumann, Zenon Rajfur, Rohan P. Choraghe |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
RHOA Innate immune system Stress fiber biology Chemistry Phagocytosis media_common.quotation_subject Pattern recognition receptor biology.organism_classification 3. Good health Cell biology 03 medical and health sciences 0302 clinical medicine biology.protein Src family kinase Candida albicans Internalization 030304 developmental biology 030215 immunology media_common |
| DOI: | 10.1101/663526 |
| Popis: | Dectin-1 is an innate immune pattern recognition receptor which recognizes β-glucan on theCandida albicans(C. albicans) cell wall. Recognition of β-glucan by immune cells leads to phagocytosis, oxidative burst, cytokine and chemokine production. We looked for specific mechanisms that coordinate phagocytosis downstream of Dectin-1 leading to actin reorganization and internalization of fungus. We found that stimulation of Dectin-1 by soluble β-glucan leads to mechanical force generation and areal contraction in Dectin-1 transfected HEK-293 cells and M1 macrophages. With inhibitor studies, we found this force generation is a SYK-independent, SFK (SRC Family Kinase)-dependent process mediated through the RHOA-ROCK-MLC pathway. We confirmed activation of RHOA downstream of Dectin-1 using G-LISA and stress fiber formation. Through phagocytosis assays, we found direct evidence for importance of RHOA-ROCK-MLC pathway in process of phagocytosis ofC. albicans. In conclusion, we found evidence for RHOA-ROCK-MLC mediated mechanical force generation downstream of Dectin-1 forC. albicansphagocytosis. |
| Databáze: | OpenAIRE |
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