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SH3‐class Ras guanine nucleotide exchange factors are essential for Aspergillus fumigatus invasive growth

Proper hyphal morphogenesis is essential for the establishment and progression of invasive disease caused by filamentous fungi. In the human pathogen Aspergillus fumigatus, signalling cascades driven by Ras and Ras‐like proteins orchestrate a wide variety of cellular processes required for hyphal gr...

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Autores principales: Martin‐Vicente, Adela, Souza, Ana Camila Oliveira, Al Abdallah, Qusai, Ge, Wenbo, Fortwendel, Jarrod R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522298/
https://www.ncbi.nlm.nih.gov/pubmed/30698898
http://dx.doi.org/10.1111/cmi.13013
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author Martin‐Vicente, Adela
Souza, Ana Camila Oliveira
Al Abdallah, Qusai
Ge, Wenbo
Fortwendel, Jarrod R.
author_facet Martin‐Vicente, Adela
Souza, Ana Camila Oliveira
Al Abdallah, Qusai
Ge, Wenbo
Fortwendel, Jarrod R.
author_sort Martin‐Vicente, Adela
collection PubMed
description Proper hyphal morphogenesis is essential for the establishment and progression of invasive disease caused by filamentous fungi. In the human pathogen Aspergillus fumigatus, signalling cascades driven by Ras and Ras‐like proteins orchestrate a wide variety of cellular processes required for hyphal growth. For activation, these proteins require interactions with Ras‐subfamily‐specific guanine nucleotide exchange factors (RasGEFs). Although Ras‐protein networks are essential for virulence in all pathogenic fungi, the importance of RasGEF proteins is largely unexplored. A. fumigatus encodes four putative RasGEFs that represent three separate classes of RasGEF proteins (SH3‐, Ras guanyl nucleotide‐releasing protein [RasGRP]–, and LTE‐class), each with fungus‐specific attributes. Here, we show that the SH3‐class and RasGRP‐class RasGEFs are required for properly timed polarity establishment during early growth and branch emergence as well as for cell wall stability. Further, we show that SH3‐class RasGEF activity is essential for polarity establishment and maintenance, a phenotype that is, at least, partially independent of the major A. fumigatus Ras proteins, RasA and RasB. Finally, loss of both SH3‐class RasGEFs resulted in avirulence in multiple models of invasive aspergillosis. Together, our findings suggest that RasGEF activity is essential for the integration of multiple signalling networks to drive invasive growth in A. fumigatus.
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spelling pubmed-65222982019-07-10 SH3‐class Ras guanine nucleotide exchange factors are essential for Aspergillus fumigatus invasive growth Martin‐Vicente, Adela Souza, Ana Camila Oliveira Al Abdallah, Qusai Ge, Wenbo Fortwendel, Jarrod R. Cell Microbiol Research Articles Proper hyphal morphogenesis is essential for the establishment and progression of invasive disease caused by filamentous fungi. In the human pathogen Aspergillus fumigatus, signalling cascades driven by Ras and Ras‐like proteins orchestrate a wide variety of cellular processes required for hyphal growth. For activation, these proteins require interactions with Ras‐subfamily‐specific guanine nucleotide exchange factors (RasGEFs). Although Ras‐protein networks are essential for virulence in all pathogenic fungi, the importance of RasGEF proteins is largely unexplored. A. fumigatus encodes four putative RasGEFs that represent three separate classes of RasGEF proteins (SH3‐, Ras guanyl nucleotide‐releasing protein [RasGRP]–, and LTE‐class), each with fungus‐specific attributes. Here, we show that the SH3‐class and RasGRP‐class RasGEFs are required for properly timed polarity establishment during early growth and branch emergence as well as for cell wall stability. Further, we show that SH3‐class RasGEF activity is essential for polarity establishment and maintenance, a phenotype that is, at least, partially independent of the major A. fumigatus Ras proteins, RasA and RasB. Finally, loss of both SH3‐class RasGEFs resulted in avirulence in multiple models of invasive aspergillosis. Together, our findings suggest that RasGEF activity is essential for the integration of multiple signalling networks to drive invasive growth in A. fumigatus. John Wiley and Sons Inc. 2019-02-15 2019-06 /pmc/articles/PMC6522298/ /pubmed/30698898 http://dx.doi.org/10.1111/cmi.13013 Text en © 2019 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Martin‐Vicente, Adela
Souza, Ana Camila Oliveira
Al Abdallah, Qusai
Ge, Wenbo
Fortwendel, Jarrod R.
SH3‐class Ras guanine nucleotide exchange factors are essential for Aspergillus fumigatus invasive growth
title SH3‐class Ras guanine nucleotide exchange factors are essential for Aspergillus fumigatus invasive growth
title_full SH3‐class Ras guanine nucleotide exchange factors are essential for Aspergillus fumigatus invasive growth
title_fullStr SH3‐class Ras guanine nucleotide exchange factors are essential for Aspergillus fumigatus invasive growth
title_full_unstemmed SH3‐class Ras guanine nucleotide exchange factors are essential for Aspergillus fumigatus invasive growth
title_short SH3‐class Ras guanine nucleotide exchange factors are essential for Aspergillus fumigatus invasive growth
title_sort sh3‐class ras guanine nucleotide exchange factors are essential for aspergillus fumigatus invasive growth
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522298/
https://www.ncbi.nlm.nih.gov/pubmed/30698898
http://dx.doi.org/10.1111/cmi.13013
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