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Connecdenn 3/DENND1C binds actin linking Rab35 activation to the actin cytoskeleton

The small GTPase Rab35 regulates endosomal membrane trafficking but also recruits effectors that modulate actin assembly and organization. Differentially expressed in normal and neoplastic cells (DENN)–domain proteins are a newly identified class of Rab guanine-nucleotide exchange factors (GEFs) tha...

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Autores principales: Marat, Andrea L., Ioannou, Maria S., McPherson, Peter S.
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/PMC3248895/
https://www.ncbi.nlm.nih.gov/pubmed/22072793
http://dx.doi.org/10.1091/mbc.E11-05-0474
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author Marat, Andrea L.
Ioannou, Maria S.
McPherson, Peter S.
author_facet Marat, Andrea L.
Ioannou, Maria S.
McPherson, Peter S.
author_sort Marat, Andrea L.
collection PubMed
description The small GTPase Rab35 regulates endosomal membrane trafficking but also recruits effectors that modulate actin assembly and organization. Differentially expressed in normal and neoplastic cells (DENN)–domain proteins are a newly identified class of Rab guanine-nucleotide exchange factors (GEFs) that are grouped into eight families, each activating a common Rab. The members of one family, connecdenn 1–3/DENND1A–C, are all GEFs for Rab35. Why Rab35 requires multiple GEFs is unknown. We demonstrate that connecdenn 3 uses a unique C-terminal motif, a feature not found in connecdenn 1 or 2, to directly bind actin. This interaction couples Rab35 activation to the actin cytoskeleton, resulting in dramatic changes in cell shape, notably the formation of protrusive membrane extensions. These alterations are specific to Rab35 activated by connecdenn 3 and require both the actin-binding motif and N-terminal DENN domain, which harbors the GEF activity. It was previously demonstrated that activated Rab35 recruits the actin-bundling protein fascin to actin, but the relevant GEF for this activity was unknown. We demonstrate that connecdenn 3 and Rab35 colocalize with fascin and actin filaments, suggesting that connecdenn 3 is the relevant GEF. Thus, whereas connecdenn 1 and 2 activate Rab35 for endosomal trafficking, connecdenn 3 uniquely activates Rab35 for its role in actin regulation.
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spelling pubmed-32488952012-03-16 Connecdenn 3/DENND1C binds actin linking Rab35 activation to the actin cytoskeleton Marat, Andrea L. Ioannou, Maria S. McPherson, Peter S. Mol Biol Cell Articles The small GTPase Rab35 regulates endosomal membrane trafficking but also recruits effectors that modulate actin assembly and organization. Differentially expressed in normal and neoplastic cells (DENN)–domain proteins are a newly identified class of Rab guanine-nucleotide exchange factors (GEFs) that are grouped into eight families, each activating a common Rab. The members of one family, connecdenn 1–3/DENND1A–C, are all GEFs for Rab35. Why Rab35 requires multiple GEFs is unknown. We demonstrate that connecdenn 3 uses a unique C-terminal motif, a feature not found in connecdenn 1 or 2, to directly bind actin. This interaction couples Rab35 activation to the actin cytoskeleton, resulting in dramatic changes in cell shape, notably the formation of protrusive membrane extensions. These alterations are specific to Rab35 activated by connecdenn 3 and require both the actin-binding motif and N-terminal DENN domain, which harbors the GEF activity. It was previously demonstrated that activated Rab35 recruits the actin-bundling protein fascin to actin, but the relevant GEF for this activity was unknown. We demonstrate that connecdenn 3 and Rab35 colocalize with fascin and actin filaments, suggesting that connecdenn 3 is the relevant GEF. Thus, whereas connecdenn 1 and 2 activate Rab35 for endosomal trafficking, connecdenn 3 uniquely activates Rab35 for its role in actin regulation. The American Society for Cell Biology 2012-01-01 /pmc/articles/PMC3248895/ /pubmed/22072793 http://dx.doi.org/10.1091/mbc.E11-05-0474 Text en © 2012 Marat 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
Marat, Andrea L.
Ioannou, Maria S.
McPherson, Peter S.
Connecdenn 3/DENND1C binds actin linking Rab35 activation to the actin cytoskeleton
title Connecdenn 3/DENND1C binds actin linking Rab35 activation to the actin cytoskeleton
title_full Connecdenn 3/DENND1C binds actin linking Rab35 activation to the actin cytoskeleton
title_fullStr Connecdenn 3/DENND1C binds actin linking Rab35 activation to the actin cytoskeleton
title_full_unstemmed Connecdenn 3/DENND1C binds actin linking Rab35 activation to the actin cytoskeleton
title_short Connecdenn 3/DENND1C binds actin linking Rab35 activation to the actin cytoskeleton
title_sort connecdenn 3/dennd1c binds actin linking rab35 activation to the actin cytoskeleton
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248895/
https://www.ncbi.nlm.nih.gov/pubmed/22072793
http://dx.doi.org/10.1091/mbc.E11-05-0474
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