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Published on: April 13, 2017
Morphofunctional programming of microglia requires distinct roles of type II myosins
Pedro Neves Melo1,2, Mariana Souza da Silveira1,3, Inês Mendes Pinto1,4
1Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Porto, Portugal.
Abstract:
The ramified morphology of microglia and the dynamics of their membrane protrusions are essential for their functions in central nervous system development, homeostasis, and disease. Although their ability to change and control shape critically depends on the actin and actomyosin cytoskeleton, the underlying regulatory mechanisms remain largely unknown. In this study, we systematically analyzed the actomyosin cytoskeleton and regulators downstream of the small GTPase RhoA in the control of microglia shape and function. Our results reveal that (i) Myh9 controls cortical tension levels and affects microglia protrusion formation, (ii) cofilin-mediated maintenance of actin turnover regulates microglia protrusion extension, and (iii) Myh10 influences microglia inflammatory activation. Overall we uncover molecular pathways that regulate microglia morphology and identify type-II myosins as important regulators of microglia biology with differential roles in the control of cell shape (Myh9) and functions (Myh10).
Insights
Microglia shape and function rely on the actomyosin cytoskeleton. This study identifies type-II myosins (Myh9, Myh10) as key regulators of microglia morphology and inflammatory responses.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Microglia, the immune cells of the central nervous system, possess a ramified morphology crucial for their functions.
- The actin and actomyosin cytoskeleton regulate microglia shape and membrane protrusion dynamics.
- Regulatory mechanisms controlling microglia cytoskeleton remain largely unknown.
Purpose of the Study:
- To systematically analyze the actomyosin cytoskeleton and RhoA signaling pathways in controlling microglia shape and function.
- To identify specific molecular regulators of microglia morphology and inflammatory activation.
Main Methods:
- Systematic analysis of the actomyosin cytoskeleton in microglia.
- Investigation of RhoA signaling pathway effectors.
- Assessment of myosin heavy chain 9 (Myh9) and myosin heavy chain 10 (Myh10) roles.
Main Results:
- Myh9 controls cortical tension and microglia protrusion formation.
- Cofilin-mediated actin turnover is essential for microglia protrusion extension.
- Myh10 influences microglia inflammatory activation.
- Type-II myosins exhibit differential roles in regulating microglia cell shape and function.
Conclusions:
- Uncovered molecular pathways regulating microglia morphology.
- Identified type-II myosins as critical regulators of microglia biology.
- Demonstrated distinct roles for Myh9 in cell shape and Myh10 in inflammatory function.
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