The Putative Guanine Nucleotide Exchange Factor RicA Mediates Upstream Signaling for Growth and Development in Aspergillus

Kwon, Nak‐Jung; Park, Hee Soo; Jung, Seunho; Kim, Sun Chang; Yu, Jae Hyuk

doi:10.1128/ec.00255-12

Cited by 25 publications

(16 citation statements)

References 77 publications

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“…In Neurospora crassa, disruption of the RIC8 gene results in a phenotype similar to that of G␣ gna1 and G␣ gna3 mutants (25), and expression of a dominant-active GNA3 in the ric8 deletion mutant leads to a significant increase in conidial germination (26). Deletion of the ricA gene (a RIC8 homolog) leads to impaired colony growth and total or partial loss of asexual sporulation in Aspergillus nidulans and Aspergillus fumigatus, respectively (27). In the rice blast fungus Magnaporthe oryzae, MoRic8, a Ric8 homolog, interacts with the G␣ protein MoMagB to regulate appressorial differentiation (28).…”

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confidence: 99%

A Ric8/Synembryn Homolog Promotes Gpa1 and Gpa2 Activation To Respectively Regulate Cyclic AMP and Pheromone Signaling in Cryptococcus neoformans

2014

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The G protein ␣ subunits Gpa1, Gpa2, and Gpa3 mediate signal transduction and are important in the growth and virulence of Cryptococcus neoformans. To understand how Gpa1 functions without a conventional G␤ subunit, we characterized a resistance to inhibitors of cholinesterase 8 (Ric8) homolog from C. neoformans, which shares amino acid sequence homology with other Ric8 proteins that exhibit guanine nucleotide exchange factor (GEF) activity toward G␣. We found that the ric8 mutant was reduced in capsule size and melanin formation, which could be suppressed by cyclic AMP (cAMP) supplementation or by introducing the activated GPA1 Q284L allele. Consistent with the fact that Ric8 participates in cAMP signaling to regulate virulence, the ric8 mutant was attenuated in virulence toward mice. Interestingly, disruption of RIC8 also resulted in opposing effects on pheromone signaling, as the ric8 mutant showed reduced mating but an enhanced ability to induce the pheromone response in the mating partner. To identify Ric8 functional mechanisms, we examined the interactions between Ric8 and the three G␣ proteins. Ric8 interacted with Gpa1 and Gpa2, but not Gpa3. The presence of Gpa1 Q284L negatively affected its interaction with Ric8, whereas the activated Gpa2 Q203L allele abolished the interaction. Collectively, these findings suggest that Ric8 functions as a GEF to facilitate the activation of Gpa1-cAMP signaling and to promote Gpa2, affecting mating efficiency. Our study highlights the distinct and conserved characteristics associated with G protein signaling and contributes to our overall understanding of how G protein ␣ subunits function with or without a canonical G␤ partner in C. neoformans.

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confidence: 99%

A Ric8/Synembryn Homolog Promotes Gpa1 and Gpa2 Activation To Respectively Regulate Cyclic AMP and Pheromone Signaling in Cryptococcus neoformans

2014

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“…nidulans grown on solid medium were similar to those observed for WT strains [11], [13], those of the Δ cpcB mutant were severely impaired resulting in extremely small colonies (Figs. 2A & 3A), which resembles the mutant lacking the putative GEF RicA [56]. In contrast, in A. fumigatus , whereas the cpcB deletion mutant exhibited radial growth that is about 80% WT, the Δ AfusfaD and Δ AfugpgA mutants showed extremely impaired hyphal growth on solid medium (Fig.…”

Section: Discussionmentioning

confidence: 85%

“…Likewise, CpcB might be necessary for the stabilization of one or more of Gα proteins in Aspergillus , and a prolonged activation of FadA and GanB by the removal of the cognate negative regulator and the absence of CpcB may cause effects similar to a total lack of heterotrimeric G protein signaling. In this regard, it is noteworthy that the deletion of the putative GEF RicA caused severely impaired growth and the total absence of conidiation in A. nidulans [56].…”

Section: Discussionmentioning

confidence: 98%

Gβ-Like CpcB Plays a Crucial Role for Growth and Development of Aspergillus nidulans and Aspergillus fumigatus

et al. 2013

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Growth, development, virulence and secondary metabolism in fungi are governed by heterotrimeric G proteins (G proteins). A Gβ-like protein called Gib2 has been shown to function as an atypical Gβ in Gpa1-cAMP signaling in Cryptococcus neoformans. We found that the previously reported CpcB (cross pathway control B) protein is the ortholog of Gib2 in Aspergillus nidulans and Aspergillus fumigatus. In this report, we further characterize the roles of CpcB in governing growth, development and toxigenesis in the two aspergilli. The deletion of cpcB results in severely impaired cellular growth, delayed spore germination, and defective asexual sporulation (conidiation) in both aspergilli. Moreover, CpcB is necessary for proper expression of the key developmental activator brlA during initiation and progression of conidiation in A. nidulans and A. fumigatus. Somewhat in accordance with the previous study, the absence of cpcB results in the formation of fewer, but not micro-, cleistothecia in A. nidulans in the presence of wild type veA, an essential activator of sexual development. However, the cpcB deletion mutant cleistothecia contain no ascospores, validating that CpcB is required for progression and completion of sexual fruiting including ascosporogenesis. Furthermore, unlike the canonical GβSfaD, CpcB is not needed for the biosynthesis of the mycotoxin sterigmatocystin (ST) as the cpcB null mutant produced reduced amount of ST with unaltered STC gene expression. However, in A. fumigatus, the deletion of cpcB results in the blockage of gliotoxin (GT) production. Further genetic analyses in A. nidulans indicate that CpcB may play a central role in vegetative growth, which might be independent of FadA- and GanB-mediated signaling. A speculative model summarizing the roles of CpcB in conjunction with SfaD in A. nidulans is presented.

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“…RicA, which is a putative GDP/GTP exchange factor for G-proteins in A. nidulans and A. fumigatus, can physically interact with GanB, mediates growth and developmental signaling primarily through GanB and PkaA in A. nidulans. The deletion of ricA resulted in severely impaired colony growth and decreased conidiation [78]. Loss of function mutations of fluG and flbA resulted in the appearance of undifferentiated mycelia in "fluffy" colonies.…”

Section: Regulation Of the Switch From Vegetative Growth To Conidiationmentioning

confidence: 99%

Functions, Cooperation, and Interplays of the Vegetative Growth Signaling Pathway in theAspergilli

Pusztahelyi

Pócsi

2013

Journal of Mycology

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Knowledge on the functions, cooperation, and interplays of the signaling and regulatory pathways of filamentous fungi is crucial when their industrial performance is improved or when new-type antifungals are developed. Many research groups aim at a deeper understanding of vegetative growth signaling because this cascade also influences other important physiological processes including asexual and sexual developments, autolysis and apoptotic cell death as well as the production of a wide array of important secondary metabolites. This review also focuses on how this signaling pathway is interconnected with other signaling cascades setting up a robust but delicately regulated signaling network in theAspergilli.

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The Putative Guanine Nucleotide Exchange Factor RicA Mediates Upstream Signaling for Growth and Development in Aspergillus

Cited by 25 publications

References 77 publications

A Ric8/Synembryn Homolog Promotes Gpa1 and Gpa2 Activation To Respectively Regulate Cyclic AMP and Pheromone Signaling in Cryptococcus neoformans

A Ric8/Synembryn Homolog Promotes Gpa1 and Gpa2 Activation To Respectively Regulate Cyclic AMP and Pheromone Signaling in Cryptococcus neoformans

Gβ-Like CpcB Plays a Crucial Role for Growth and Development of Aspergillus nidulans and Aspergillus fumigatus

Functions, Cooperation, and Interplays of the Vegetative Growth Signaling Pathway in theAspergilli

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