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

Adela Martin-Vicente, Ana Camila Oliveira Souza, Qusai Al Abdallah, Wenbo Ge, Jarrod Fortwendel

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere13013
JournalCellular Microbiology
Volume21
Issue number6
DOIs
StatePublished - Jun 1 2019

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ras Guanine Nucleotide Exchange Factors
Guanine Nucleotide Exchange Factors
Aspergillus fumigatus
ras Proteins
Growth
Fungi
Nucleotides
Proteins
Aspergillosis
Morphogenesis
Cell Wall
Virulence
Disease Progression
Maintenance

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Virology

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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.

In: Cellular Microbiology, Vol. 21, No. 6, e13013, 01.06.2019.

Research output: Contribution to journalArticle

Martin-Vicente, Adela ; Souza, Ana Camila Oliveira ; Al Abdallah, Qusai ; Ge, Wenbo ; Fortwendel, Jarrod. / SH3-class Ras guanine nucleotide exchange factors are essential for Aspergillus fumigatus invasive growth. In: Cellular Microbiology. 2019 ; Vol. 21, No. 6.
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