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The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways

Bacterial toxins and effector proteins hijack eukaryotic enzymes that are spatially localized and display rapid signaling kinetics. However, the molecular mechanisms by which virulence factors engage highly dynamic substrates in the host cell environment are poorly understood. Here, we demonstrate t...

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Autores principales: Alto, Neal M., Weflen, Andrew W., Rardin, Matthew J., Yarar, Defne, Lazar, Cheri S., Tonikian, Raffi, Koller, Antonius, Taylor, Susan S., Boone, Charles, Sidhu, Sachdev S., Schmid, Sandra L., Hecht, Gail A., Dixon, Jack E.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064658/
https://www.ncbi.nlm.nih.gov/pubmed/17893247
http://dx.doi.org/10.1083/jcb.200705021
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author Alto, Neal M.
Weflen, Andrew W.
Rardin, Matthew J.
Yarar, Defne
Lazar, Cheri S.
Tonikian, Raffi
Koller, Antonius
Taylor, Susan S.
Boone, Charles
Sidhu, Sachdev S.
Schmid, Sandra L.
Hecht, Gail A.
Dixon, Jack E.
author_facet Alto, Neal M.
Weflen, Andrew W.
Rardin, Matthew J.
Yarar, Defne
Lazar, Cheri S.
Tonikian, Raffi
Koller, Antonius
Taylor, Susan S.
Boone, Charles
Sidhu, Sachdev S.
Schmid, Sandra L.
Hecht, Gail A.
Dixon, Jack E.
author_sort Alto, Neal M.
collection PubMed
description Bacterial toxins and effector proteins hijack eukaryotic enzymes that are spatially localized and display rapid signaling kinetics. However, the molecular mechanisms by which virulence factors engage highly dynamic substrates in the host cell environment are poorly understood. Here, we demonstrate that the enteropathogenic Escherichia coli (EPEC) type III effector protein EspF nucleates a multiprotein signaling complex composed of eukaryotic sorting nexin 9 (SNX9) and neuronal Wiskott-Aldrich syndrome protein (N-WASP). We demonstrate that a specific and high affinity association between EspF and SNX9 induces membrane remodeling in host cells. These membrane-remodeling events are directly coupled to N-WASP/Arp2/3–mediated actin nucleation. In addition to providing a biochemical mechanism of EspF function, we find that EspF dynamically localizes to membrane-trafficking organelles in a spatiotemporal pattern that correlates with SNX9 and N-WASP activity in living cells. Thus, our findings suggest that the EspF-dependent assembly of SNX9 and N-WASP represents a novel form of signaling mimicry used to promote EPEC pathogenesis and gastrointestinal disease.
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spelling pubmed-20646582008-03-24 The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways Alto, Neal M. Weflen, Andrew W. Rardin, Matthew J. Yarar, Defne Lazar, Cheri S. Tonikian, Raffi Koller, Antonius Taylor, Susan S. Boone, Charles Sidhu, Sachdev S. Schmid, Sandra L. Hecht, Gail A. Dixon, Jack E. J Cell Biol Research Articles Bacterial toxins and effector proteins hijack eukaryotic enzymes that are spatially localized and display rapid signaling kinetics. However, the molecular mechanisms by which virulence factors engage highly dynamic substrates in the host cell environment are poorly understood. Here, we demonstrate that the enteropathogenic Escherichia coli (EPEC) type III effector protein EspF nucleates a multiprotein signaling complex composed of eukaryotic sorting nexin 9 (SNX9) and neuronal Wiskott-Aldrich syndrome protein (N-WASP). We demonstrate that a specific and high affinity association between EspF and SNX9 induces membrane remodeling in host cells. These membrane-remodeling events are directly coupled to N-WASP/Arp2/3–mediated actin nucleation. In addition to providing a biochemical mechanism of EspF function, we find that EspF dynamically localizes to membrane-trafficking organelles in a spatiotemporal pattern that correlates with SNX9 and N-WASP activity in living cells. Thus, our findings suggest that the EspF-dependent assembly of SNX9 and N-WASP represents a novel form of signaling mimicry used to promote EPEC pathogenesis and gastrointestinal disease. The Rockefeller University Press 2007-09-24 /pmc/articles/PMC2064658/ /pubmed/17893247 http://dx.doi.org/10.1083/jcb.200705021 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Alto, Neal M.
Weflen, Andrew W.
Rardin, Matthew J.
Yarar, Defne
Lazar, Cheri S.
Tonikian, Raffi
Koller, Antonius
Taylor, Susan S.
Boone, Charles
Sidhu, Sachdev S.
Schmid, Sandra L.
Hecht, Gail A.
Dixon, Jack E.
The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways
title The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways
title_full The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways
title_fullStr The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways
title_full_unstemmed The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways
title_short The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways
title_sort type iii effector espf coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064658/
https://www.ncbi.nlm.nih.gov/pubmed/17893247
http://dx.doi.org/10.1083/jcb.200705021
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