Differential support of aspergillus fumigatus morphogenesis by yeast and human actins

Lawrence L. LeClaire, Jarrod Fortwendel

Research output: Contribution to journalArticle

Abstract

The actin cytoskeleton is highly conserved among eukaryotes and is essential for cellular processes regulating growth and differentiation. In fungi, filamentous actin (F-Actin) orchestrates hyphal tip structure and extension via organization of exocytic and endocytic processes at the hyphal tip. Although highly conserved, there are key differences among actins of fungal species as well as between mammalian and fungal actins. For example, the Factin stabilizing molecules, phalloidin and jasplakinolide, bind to actin structures in yeast and human cells, whereas phalloidin does not bind actin structures of Aspergillus. These discrepancies suggest structural differences between Aspergillus actin filaments and those of human and yeast cells. Additionally, fungal actin kinetics are much faster than those of humans, displaying 5-fold faster nucleation and 40-fold faster nucleotide exchange rates. Limited published studies suggest that these faster actin kinetics are required for normal growth and morphogenesis of yeast cells. In the current work, we show that replacement of Aspergillus actin with yeast actin generates a morphologically normal strain, suggesting that Aspergillus actin kinetics are similar to those of yeast. In contrast to wild type A. fumigatus, F-Actin in this strain binds phalloidin, and pharmacological stabilization of these actin structures with jasplakinolide inhibits germination and alters morphogenesis in a dosedependent manner. We also show that human β-Actin cannot support Aspergillus viability, even though the amino acid sequences of human and Aspergillus actins are 89.3%identical. Our findings show that minor differences in actin protein sequence account for loss of phalloidin and jasplakinolide sensitivity in Aspergillus species.

Original languageEnglish (US)
Article numbere0142535
JournalPloS one
Volume10
Issue number11
DOIs
StatePublished - Nov 10 2015

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Aspergillus fumigatus
Aspergillus
Morphogenesis
Yeast
morphogenesis
actin
Actins
Yeasts
yeasts
jasplakinolide
Phalloidine
microfilaments
Actin Cytoskeleton
kinetics
Cells
Kinetics
amino acid sequences
cells
Growth
Germination

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Differential support of aspergillus fumigatus morphogenesis by yeast and human actins. / LeClaire, Lawrence L.; Fortwendel, Jarrod.

In: PloS one, Vol. 10, No. 11, e0142535, 10.11.2015.

Research output: Contribution to journalArticle

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