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Mammalian target of rapamycin and Rictor control neutrophil chemotaxis by regulating Rac/Cdc42 activity and the actin cytoskeleton

Chemotaxis allows neutrophils to seek out sites of infection and inflammation. The asymmetric accumulation of filamentous actin (F-actin) at the leading edge provides the driving force for protrusion and is essential for the development and maintenance of neutrophil polarity. The mechanism that gove...

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Autores principales: He, Yuan, Li, Dong, Cook, Sara L., Yoon, Mee-Sup, Kapoor, Ashish, Rao, Christopher V., Kenis, Paul J. A., Chen, Jie, Wang, Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814157/
https://www.ncbi.nlm.nih.gov/pubmed/24006489
http://dx.doi.org/10.1091/mbc.E13-07-0405
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author He, Yuan
Li, Dong
Cook, Sara L.
Yoon, Mee-Sup
Kapoor, Ashish
Rao, Christopher V.
Kenis, Paul J. A.
Chen, Jie
Wang, Fei
author_facet He, Yuan
Li, Dong
Cook, Sara L.
Yoon, Mee-Sup
Kapoor, Ashish
Rao, Christopher V.
Kenis, Paul J. A.
Chen, Jie
Wang, Fei
author_sort He, Yuan
collection PubMed
description Chemotaxis allows neutrophils to seek out sites of infection and inflammation. The asymmetric accumulation of filamentous actin (F-actin) at the leading edge provides the driving force for protrusion and is essential for the development and maintenance of neutrophil polarity. The mechanism that governs actin cytoskeleton dynamics and assembly in neutrophils has been extensively explored and is still not fully understood. By using neutrophil-like HL-60 cells, we describe a pivotal role for Rictor, a component of mammalian target of rapamycin complex 2 (mTORC2), in regulating assembly of the actin cytoskeleton during neutrophil chemotaxis. Depletion of mTOR and Rictor, but not Raptor, impairs actin polymerization, leading-edge establishment, and directional migration in neutrophils stimulated with chemoattractants. Of interest, depletion of mSin1, an integral component of mTORC2, causes no detectable defects in neutrophil polarity and chemotaxis. In addition, experiments with chemical inhibition and kinase-dead mutants indicate that mTOR kinase activity and AKT phosphorylation are dispensable for chemotaxis. Instead, our results suggest that the small Rho GTPases Rac and Cdc42 serve as downstream effectors of Rictor to regulate actin assembly and organization in neutrophils. Together our findings reveal an mTORC2- and mTOR kinase–independent function and mechanism of Rictor in the regulation of neutrophil chemotaxis.
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spelling pubmed-38141572014-01-16 Mammalian target of rapamycin and Rictor control neutrophil chemotaxis by regulating Rac/Cdc42 activity and the actin cytoskeleton He, Yuan Li, Dong Cook, Sara L. Yoon, Mee-Sup Kapoor, Ashish Rao, Christopher V. Kenis, Paul J. A. Chen, Jie Wang, Fei Mol Biol Cell Articles Chemotaxis allows neutrophils to seek out sites of infection and inflammation. The asymmetric accumulation of filamentous actin (F-actin) at the leading edge provides the driving force for protrusion and is essential for the development and maintenance of neutrophil polarity. The mechanism that governs actin cytoskeleton dynamics and assembly in neutrophils has been extensively explored and is still not fully understood. By using neutrophil-like HL-60 cells, we describe a pivotal role for Rictor, a component of mammalian target of rapamycin complex 2 (mTORC2), in regulating assembly of the actin cytoskeleton during neutrophil chemotaxis. Depletion of mTOR and Rictor, but not Raptor, impairs actin polymerization, leading-edge establishment, and directional migration in neutrophils stimulated with chemoattractants. Of interest, depletion of mSin1, an integral component of mTORC2, causes no detectable defects in neutrophil polarity and chemotaxis. In addition, experiments with chemical inhibition and kinase-dead mutants indicate that mTOR kinase activity and AKT phosphorylation are dispensable for chemotaxis. Instead, our results suggest that the small Rho GTPases Rac and Cdc42 serve as downstream effectors of Rictor to regulate actin assembly and organization in neutrophils. Together our findings reveal an mTORC2- and mTOR kinase–independent function and mechanism of Rictor in the regulation of neutrophil chemotaxis. The American Society for Cell Biology 2013-11-01 /pmc/articles/PMC3814157/ /pubmed/24006489 http://dx.doi.org/10.1091/mbc.E13-07-0405 Text en © 2013 He et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
He, Yuan
Li, Dong
Cook, Sara L.
Yoon, Mee-Sup
Kapoor, Ashish
Rao, Christopher V.
Kenis, Paul J. A.
Chen, Jie
Wang, Fei
Mammalian target of rapamycin and Rictor control neutrophil chemotaxis by regulating Rac/Cdc42 activity and the actin cytoskeleton
title Mammalian target of rapamycin and Rictor control neutrophil chemotaxis by regulating Rac/Cdc42 activity and the actin cytoskeleton
title_full Mammalian target of rapamycin and Rictor control neutrophil chemotaxis by regulating Rac/Cdc42 activity and the actin cytoskeleton
title_fullStr Mammalian target of rapamycin and Rictor control neutrophil chemotaxis by regulating Rac/Cdc42 activity and the actin cytoskeleton
title_full_unstemmed Mammalian target of rapamycin and Rictor control neutrophil chemotaxis by regulating Rac/Cdc42 activity and the actin cytoskeleton
title_short Mammalian target of rapamycin and Rictor control neutrophil chemotaxis by regulating Rac/Cdc42 activity and the actin cytoskeleton
title_sort mammalian target of rapamycin and rictor control neutrophil chemotaxis by regulating rac/cdc42 activity and the actin cytoskeleton
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814157/
https://www.ncbi.nlm.nih.gov/pubmed/24006489
http://dx.doi.org/10.1091/mbc.E13-07-0405
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