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Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration

Migratory immune cells use intracellular signaling networks to generate and orient spatially polarized responses to extracellular cues. The monomeric G protein Cdc42 is believed to play an important role in controlling the polarized responses, but it has been difficult to determine directly the cons...

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Detalles Bibliográficos
Autores principales: O’Neill, Patrick R., Kalyanaraman, Vani, Gautam, N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850032/
https://www.ncbi.nlm.nih.gov/pubmed/26941336
http://dx.doi.org/10.1091/mbc.E15-12-0832
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author O’Neill, Patrick R.
Kalyanaraman, Vani
Gautam, N.
author_facet O’Neill, Patrick R.
Kalyanaraman, Vani
Gautam, N.
author_sort O’Neill, Patrick R.
collection PubMed
description Migratory immune cells use intracellular signaling networks to generate and orient spatially polarized responses to extracellular cues. The monomeric G protein Cdc42 is believed to play an important role in controlling the polarized responses, but it has been difficult to determine directly the consequences of localized Cdc42 activation within an immune cell. Here we used subcellular optogenetics to determine how Cdc42 activation at one side of a cell affects both cell behavior and dynamic molecular responses throughout the cell. We found that localized Cdc42 activation is sufficient to generate polarized signaling and directional cell migration. The optically activated region becomes the leading edge of the cell, with Cdc42 activating Rac and generating membrane protrusions driven by the actin cytoskeleton. Cdc42 also exerts long-range effects that cause myosin accumulation at the opposite side of the cell and actomyosin-mediated retraction of the cell rear. This process requires the RhoA-activated kinase ROCK, suggesting that Cdc42 activation at one side of a cell triggers increased RhoA signaling at the opposite side. Our results demonstrate how dynamic, subcellular perturbation of an individual signaling protein can help to determine its role in controlling polarized cellular responses.
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spelling pubmed-48500322016-07-16 Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration O’Neill, Patrick R. Kalyanaraman, Vani Gautam, N. Mol Biol Cell Articles Migratory immune cells use intracellular signaling networks to generate and orient spatially polarized responses to extracellular cues. The monomeric G protein Cdc42 is believed to play an important role in controlling the polarized responses, but it has been difficult to determine directly the consequences of localized Cdc42 activation within an immune cell. Here we used subcellular optogenetics to determine how Cdc42 activation at one side of a cell affects both cell behavior and dynamic molecular responses throughout the cell. We found that localized Cdc42 activation is sufficient to generate polarized signaling and directional cell migration. The optically activated region becomes the leading edge of the cell, with Cdc42 activating Rac and generating membrane protrusions driven by the actin cytoskeleton. Cdc42 also exerts long-range effects that cause myosin accumulation at the opposite side of the cell and actomyosin-mediated retraction of the cell rear. This process requires the RhoA-activated kinase ROCK, suggesting that Cdc42 activation at one side of a cell triggers increased RhoA signaling at the opposite side. Our results demonstrate how dynamic, subcellular perturbation of an individual signaling protein can help to determine its role in controlling polarized cellular responses. The American Society for Cell Biology 2016-05-01 /pmc/articles/PMC4850032/ /pubmed/26941336 http://dx.doi.org/10.1091/mbc.E15-12-0832 Text en © 2016 O’Neill 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 for Cell Biology.
spellingShingle Articles
O’Neill, Patrick R.
Kalyanaraman, Vani
Gautam, N.
Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration
title Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration
title_full Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration
title_fullStr Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration
title_full_unstemmed Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration
title_short Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration
title_sort subcellular optogenetic activation of cdc42 controls local and distal signaling to drive immune cell migration
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850032/
https://www.ncbi.nlm.nih.gov/pubmed/26941336
http://dx.doi.org/10.1091/mbc.E15-12-0832
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