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Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling

Cells rely on the coordinated regulation of lipid phosphoinositides and Rab GTPases to define membrane compartment fates along distinct trafficking routes. The family of disease-related myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, w...

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Detalles Bibliográficos
Autores principales: Jean, Steve, Cox, Sarah, Schmidt, Eric J., Robinson, Fred L., Kiger, Amy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395661/
https://www.ncbi.nlm.nih.gov/pubmed/22648168
http://dx.doi.org/10.1091/mbc.E12-05-0375
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author Jean, Steve
Cox, Sarah
Schmidt, Eric J.
Robinson, Fred L.
Kiger, Amy
author_facet Jean, Steve
Cox, Sarah
Schmidt, Eric J.
Robinson, Fred L.
Kiger, Amy
author_sort Jean, Steve
collection PubMed
description Cells rely on the coordinated regulation of lipid phosphoinositides and Rab GTPases to define membrane compartment fates along distinct trafficking routes. The family of disease-related myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, with poorly understood functions. We found that Drosophila MTM pseudophosphatase Sbf coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. Sbf dynamically interacts with class II phosphatidylinositol 3-kinase and stably recruits Mtm to promote turnover of a PI(3)P subpool essential for endosomal trafficking. Sbf also functions as a guanine nucleotide exchange factor that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Of importance, Sbf, Mtm, and Rab21 function together, along with Rab11-mediated endosomal trafficking, to control macrophage protrusion formation. This identifies Sbf as a critical coordinator of PI(3)P and Rab21 regulation, which specifies an endosomal pathway and cortical control.
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spelling pubmed-33956612012-09-30 Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling Jean, Steve Cox, Sarah Schmidt, Eric J. Robinson, Fred L. Kiger, Amy Mol Biol Cell Articles Cells rely on the coordinated regulation of lipid phosphoinositides and Rab GTPases to define membrane compartment fates along distinct trafficking routes. The family of disease-related myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, with poorly understood functions. We found that Drosophila MTM pseudophosphatase Sbf coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. Sbf dynamically interacts with class II phosphatidylinositol 3-kinase and stably recruits Mtm to promote turnover of a PI(3)P subpool essential for endosomal trafficking. Sbf also functions as a guanine nucleotide exchange factor that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Of importance, Sbf, Mtm, and Rab21 function together, along with Rab11-mediated endosomal trafficking, to control macrophage protrusion formation. This identifies Sbf as a critical coordinator of PI(3)P and Rab21 regulation, which specifies an endosomal pathway and cortical control. The American Society for Cell Biology 2012-07-15 /pmc/articles/PMC3395661/ /pubmed/22648168 http://dx.doi.org/10.1091/mbc.E12-05-0375 Text en © 2012 Jean 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 BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Jean, Steve
Cox, Sarah
Schmidt, Eric J.
Robinson, Fred L.
Kiger, Amy
Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling
title Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling
title_full Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling
title_fullStr Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling
title_full_unstemmed Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling
title_short Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling
title_sort sbf/mtmr13 coordinates pi(3)p and rab21 regulation in endocytic control of cellular remodeling
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395661/
https://www.ncbi.nlm.nih.gov/pubmed/22648168
http://dx.doi.org/10.1091/mbc.E12-05-0375
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