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Binding to Na(+)/H(+) exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH
Enteropathogenic Escherichia coli (EPEC) strains are diarrhoeal pathogens that use a type III secretion system to translocate effector proteins into host cells in order to colonize and multiply in the human gut. Map, EspI and NleH1 are conserved EPEC effectors that possess a C-terminal class I PSD-9...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3015060/ https://www.ncbi.nlm.nih.gov/pubmed/20618342 http://dx.doi.org/10.1111/j.1462-5822.2010.01503.x |
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author | Martinez, Eric Schroeder, Gunnar N Berger, Cedric N Lee, Sau Fung Robinson, Keith S Badea, Luminita Simpson, Nandi Hall, Randy A Hartland, Elizabeth L Crepin, Valerie F Frankel, Gad |
author_facet | Martinez, Eric Schroeder, Gunnar N Berger, Cedric N Lee, Sau Fung Robinson, Keith S Badea, Luminita Simpson, Nandi Hall, Randy A Hartland, Elizabeth L Crepin, Valerie F Frankel, Gad |
author_sort | Martinez, Eric |
collection | PubMed |
description | Enteropathogenic Escherichia coli (EPEC) strains are diarrhoeal pathogens that use a type III secretion system to translocate effector proteins into host cells in order to colonize and multiply in the human gut. Map, EspI and NleH1 are conserved EPEC effectors that possess a C-terminal class I PSD-95/Disc Large/ZO-1 (PDZ)-binding motif. Using a PDZ array screen we identified Na(+)/H(+) exchanger regulatory factor 2 (NHERF2), a scaffold protein involved in tethering and recycling ion channels in polarized epithelia that contains two PDZ domains, as a common target of Map, EspI and NleH1. Using recombinant proteins and co-immunoprecipitation we confirmed that NHERF2 binds each of the effectors. We generated a HeLa cell line stably expressing HA-tagged NHERF2 and found that Map, EspI and NleH1 colocalize and interact with intracellular NHERF2 via their C-terminal PDZ-binding motif. Overexpression of NHERF2 enhanced the formation and persistence of Map-induced filopodia, accelerated the trafficking of EspI to the Golgi and diminished the anti-apoptotic activity of NleH1. The binding of multiple T3SS effectors to a single scaffold protein is unique. Our data suggest that NHERF2 may act as a plasma membrane sorting site, providing a novel regulatory mechanism to control the intracellular spatial and temporal effector protein activity. |
format | Text |
id | pubmed-3015060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-30150602011-01-08 Binding to Na(+)/H(+) exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH Martinez, Eric Schroeder, Gunnar N Berger, Cedric N Lee, Sau Fung Robinson, Keith S Badea, Luminita Simpson, Nandi Hall, Randy A Hartland, Elizabeth L Crepin, Valerie F Frankel, Gad Cell Microbiol Original Articles Enteropathogenic Escherichia coli (EPEC) strains are diarrhoeal pathogens that use a type III secretion system to translocate effector proteins into host cells in order to colonize and multiply in the human gut. Map, EspI and NleH1 are conserved EPEC effectors that possess a C-terminal class I PSD-95/Disc Large/ZO-1 (PDZ)-binding motif. Using a PDZ array screen we identified Na(+)/H(+) exchanger regulatory factor 2 (NHERF2), a scaffold protein involved in tethering and recycling ion channels in polarized epithelia that contains two PDZ domains, as a common target of Map, EspI and NleH1. Using recombinant proteins and co-immunoprecipitation we confirmed that NHERF2 binds each of the effectors. We generated a HeLa cell line stably expressing HA-tagged NHERF2 and found that Map, EspI and NleH1 colocalize and interact with intracellular NHERF2 via their C-terminal PDZ-binding motif. Overexpression of NHERF2 enhanced the formation and persistence of Map-induced filopodia, accelerated the trafficking of EspI to the Golgi and diminished the anti-apoptotic activity of NleH1. The binding of multiple T3SS effectors to a single scaffold protein is unique. Our data suggest that NHERF2 may act as a plasma membrane sorting site, providing a novel regulatory mechanism to control the intracellular spatial and temporal effector protein activity. Blackwell Publishing Ltd 2010-12 2010-08-03 /pmc/articles/PMC3015060/ /pubmed/20618342 http://dx.doi.org/10.1111/j.1462-5822.2010.01503.x Text en Copyright © 2010 Blackwell Publishing Ltd http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Original Articles Martinez, Eric Schroeder, Gunnar N Berger, Cedric N Lee, Sau Fung Robinson, Keith S Badea, Luminita Simpson, Nandi Hall, Randy A Hartland, Elizabeth L Crepin, Valerie F Frankel, Gad Binding to Na(+)/H(+) exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH |
title | Binding to Na(+)/H(+) exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH |
title_full | Binding to Na(+)/H(+) exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH |
title_fullStr | Binding to Na(+)/H(+) exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH |
title_full_unstemmed | Binding to Na(+)/H(+) exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH |
title_short | Binding to Na(+)/H(+) exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH |
title_sort | binding to na(+)/h(+) exchanger regulatory factor 2 (nherf2) affects trafficking and function of the enteropathogenic escherichia coli type iii secretion system effectors map, espi and nleh |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3015060/ https://www.ncbi.nlm.nih.gov/pubmed/20618342 http://dx.doi.org/10.1111/j.1462-5822.2010.01503.x |
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