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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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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. |
format | Online Article Text |
id | pubmed-6522298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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