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The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton

We identify a new pathway that is required for proper pseudopod formation. We show that Roco2, a leucine-rich repeat kinase 2 (LRRK2)-related Roco kinase, is activated in response to chemoattractant stimulation and helps mediate cell polarization and chemotaxis by regulating cortical F-actin polymer...

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Autores principales: Kicka, Sebastian, Shen, Zhouxin, Annesley, Sarah J., Fisher, Paul R., Lee, Susan, Briggs, Steven, Firtel, Richard A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128523/
https://www.ncbi.nlm.nih.gov/pubmed/21551065
http://dx.doi.org/10.1091/mbc.E10-12-0937
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author Kicka, Sebastian
Shen, Zhouxin
Annesley, Sarah J.
Fisher, Paul R.
Lee, Susan
Briggs, Steven
Firtel, Richard A.
author_facet Kicka, Sebastian
Shen, Zhouxin
Annesley, Sarah J.
Fisher, Paul R.
Lee, Susan
Briggs, Steven
Firtel, Richard A.
author_sort Kicka, Sebastian
collection PubMed
description We identify a new pathway that is required for proper pseudopod formation. We show that Roco2, a leucine-rich repeat kinase 2 (LRRK2)-related Roco kinase, is activated in response to chemoattractant stimulation and helps mediate cell polarization and chemotaxis by regulating cortical F-actin polymerization and pseudopod extension in a pathway that requires Rab1A. We found that Roco2 binds the small GTPase Rab1A as well as the F-actin cross-linking protein filamin (actin-binding protein 120, abp120) in vivo. We show that active Rab1A (Rab1A-GTP) is required for and regulates Roco2 kinase activity in vivo and that filamin lies downstream from Roco2 and controls pseudopod extension during chemotaxis and random cell motility. Therefore our study uncovered a new signaling pathway that involves Rab1A and controls the actin cytoskeleton and pseudopod extension, and thereby, cell polarity and motility. These findings also may have implications in the regulation of other Roco kinases, including possibly LRRK2, in metazoans.
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spelling pubmed-31285232011-09-16 The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton Kicka, Sebastian Shen, Zhouxin Annesley, Sarah J. Fisher, Paul R. Lee, Susan Briggs, Steven Firtel, Richard A. Mol Biol Cell Articles We identify a new pathway that is required for proper pseudopod formation. We show that Roco2, a leucine-rich repeat kinase 2 (LRRK2)-related Roco kinase, is activated in response to chemoattractant stimulation and helps mediate cell polarization and chemotaxis by regulating cortical F-actin polymerization and pseudopod extension in a pathway that requires Rab1A. We found that Roco2 binds the small GTPase Rab1A as well as the F-actin cross-linking protein filamin (actin-binding protein 120, abp120) in vivo. We show that active Rab1A (Rab1A-GTP) is required for and regulates Roco2 kinase activity in vivo and that filamin lies downstream from Roco2 and controls pseudopod extension during chemotaxis and random cell motility. Therefore our study uncovered a new signaling pathway that involves Rab1A and controls the actin cytoskeleton and pseudopod extension, and thereby, cell polarity and motility. These findings also may have implications in the regulation of other Roco kinases, including possibly LRRK2, in metazoans. The American Society for Cell Biology 2011-07-01 /pmc/articles/PMC3128523/ /pubmed/21551065 http://dx.doi.org/10.1091/mbc.E10-12-0937 Text en © 2011 Kicka 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
Kicka, Sebastian
Shen, Zhouxin
Annesley, Sarah J.
Fisher, Paul R.
Lee, Susan
Briggs, Steven
Firtel, Richard A.
The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton
title The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton
title_full The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton
title_fullStr The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton
title_full_unstemmed The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton
title_short The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton
title_sort lrrk2-related roco kinase roco2 is regulated by rab1a and controls the actin cytoskeleton
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128523/
https://www.ncbi.nlm.nih.gov/pubmed/21551065
http://dx.doi.org/10.1091/mbc.E10-12-0937
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