Morphogenesis: Control of Cell Types and Shape

Boyce, Kylie J.; Andrianopoulos, Alex

doi:10.1007/3-540-28135-5_1

Cited by 6 publications

(4 citation statements)

References 106 publications

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“…To more closely examine growth aberrancies, we also characterized the roles of the post-prenylation modifying enzymes in conidial germination. Germination of A. fumigatus conidia is mediated by Ras, Ras-like, and Rho proteins ( Boyce and Andrianopoulos, 2006 ; Fortwendel et al, 2011 ; Park and Yu, 2016 ). Therefore, improper processing of the Ras CAAX motif could be predicted to alter this cellular process.…”

Section: Discussionmentioning

confidence: 99%

C-terminus Proteolysis and Palmitoylation Cooperate for Optimal Plasma Membrane Localization of RasA in Aspergillus fumigatus

et al. 2018

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RasA is a major regulator of fungal morphogenesis and virulence in Aspergillus fumigatus. The proper localization of RasA to the plasma membrane is essential for the formation of invasive hyphae during infection. In yeast, the localization of Ras2p to the plasma membrane is orchestrated by several post-translational modifications (PTM) at the C-terminal CAAX box that are thought to occur in sequential order. These PTMs include: (1) CAAX motif farnesylation by the farnesyltransferase complex composed of Ram1p and Ram2p; (2) proteolysis of the -AAX residues by Rce1p or Ste24p; (3) methylation of the remaining prenylated cysteine residue by Ste14p, and; (4) palmitoylation at a single conserved cysteine residue mediated by the Erf2p/Erf4p palmitoyltransferase. We previously reported that homologs of each RasA PTM enzyme are conserved in A. fumigatus. Additionally, we delineated a major role for protein farnesylation in A. fumigatus growth and virulence. In this work, we characterize the post-prenylation processing enzymes of RasA in A. fumigatus. The genes encoding the RasA post-prenylation enzymes were first deleted and examined for their roles in growth and regulation of RasA. Only when strains lacked cppB, the A. fumigatus homologue of yeast RCE1, there was a significant reduction in fungal growth and conidial germination. In addition, cppB-deletion mutants displayed hypersensitivity to the cell wall-perturbing agents Calcofluor White and Congo Red and the cell wall biosynthesis inhibitor Caspofungin. In contrast to the previously published data in yeast, the deletion of post-prenylation modifying enzymes did not alter the plasma membrane localization or activation of RasA. To delineate the molecular mechanisms underlying these differences, we investigated the interplay between dual-palmitoylation of the RasA hypervariable region and CAAX proteolysis for stabilization of RasA at the plasma membrane. Our data indicate that, in the absence of proper CAAX proteolysis, RasA accumulation at the plasma membrane is stabilized by dual palmitoyl groups on the dual cysteine residues. Therefore, we conclude CAAX proteolysis and dual-palmitoylation of the hypervariable region is important for maintaining a stable attachment association of RasA with the plasma membrane to support optimal fungal growth and development.

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Section: Discussionmentioning

confidence: 99%

C-terminus Proteolysis and Palmitoylation Cooperate for Optimal Plasma Membrane Localization of RasA in Aspergillus fumigatus

et al. 2018

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“…In filamentous fungi this includes the elongation of GTs (Araujo-Palomares et al 2007;Harris & Momany 2004), conidial anastomosis tubes (CATs) (Read et al 2009), mature vegetative hyphae (Boyce & Andrianopoulos 2006), and hyphal branches (Harris 2008). Mechanistically, polarized growth maintenance requires continuous delivery of new plasma membrane and cell wall material to the growing tip, and of course, the continued activity of the polarity establishment machinery, including the polarisome, the F-actin cytoskeleton and exocyst complex.…”

Section: Maintenance Of Polarized Growthmentioning

confidence: 99%

Form follows function – The versatile fungal cytoskeleton

2011

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“…Dimorphic fungal pathogens must regulate both the transition and maintenance of two vegetative growth states, multicellular hyphal and unicellular yeast, as well as other morphogenetic programs such as asexual development [19] . This capacity is lost when the pakB gene is deleted from P. marneffei .…”

Section: Discussionmentioning

confidence: 99%

In Vivo Yeast Cell Morphogenesis Is Regulated by a p21-Activated Kinase in the Human Pathogen Penicillium marneffei

2009

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Pathogens have developed diverse strategies to infect their hosts and evade the host defense systems. Many pathogens reside within host phagocytic cells, thus evading much of the host immune system. For dimorphic fungal pathogens which grow in a multicellular hyphal form, a central attribute which facilitates growth inside host cells without rapid killing is the capacity to switch from the hyphal growth form to a unicellular yeast form. Blocking this transition abolishes or severely reduces pathogenicity. Host body temperature (37°C) is the most common inducer of the hyphal to yeast transition in vitro for many dimorphic fungi, and it is often assumed that this is the inducer in vivo. This work describes the identification and analysis of a new pathway involved in sensing the environment inside a host cell by a dimorphic fungal pathogen, Penicillium marneffei. The pakB gene, encoding a p21-activated kinase, defines this pathway and operates independently of known effectors in P. marneffei. Expression of pakB is upregulated in P. marneffei yeast cells isolated from macrophages but absent from in vitro cultured yeast cells produced at 37°C. Deletion of pakB leads to a failure to produce yeast cells inside macrophages but no effect in vitro at 37°C. Loss of pakB also leads to the inappropriate production of yeast cells at 25°C in vitro, and the mechanism underlying this requires the activity of the central regulator of asexual development. The data shows that this new pathway is central to eliciting the appropriate morphogenetic response by the pathogen to the host environment independently of the common temperature signal, thus clearly separating the temperature- and intracellular-dependent signaling systems.

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Morphogenesis: Control of Cell Types and Shape

Cited by 6 publications

References 106 publications

C-terminus Proteolysis and Palmitoylation Cooperate for Optimal Plasma Membrane Localization of RasA in Aspergillus fumigatus

C-terminus Proteolysis and Palmitoylation Cooperate for Optimal Plasma Membrane Localization of RasA in Aspergillus fumigatus

Form follows function – The versatile fungal cytoskeleton

In Vivo Yeast Cell Morphogenesis Is Regulated by a p21-Activated Kinase in the Human Pathogen Penicillium marneffei

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