Characterizing the role of the microtubule binding protein Bim1 in Cryptococcus neoformans

Staudt, Mark W.; Kruzel, Emilia K.; Shimizu, Kiminori; Hull, Christina M.

doi:10.1016/j.fgb.2009.12.010

Cited by 14 publications

(15 citation statements)

References 24 publications

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Section: Development Of Postmating Hyphaementioning

confidence: 99%

“…Staudt et al demonstrated a conserved role of the microtubule‐associated protein Bim1 in hyphal morphology. Crosses between bim1 Δ mutants produced unusually short and curved filaments with missegregated nuclei (Staudt et al , 2010). Similarly, in Schizophyllum commune , nuclear migration was associated with microtubule tracks and microtubule‐associated motors (Raudaskoski, 1998).…”

Section: Development Of Postmating Hyphaementioning

confidence: 99%

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Profiling a killer, the development ofCryptococcus neoformans

Kozubowski

Heitman

2012

FEMS Microbiol Rev

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The ability of fungi to transition between unicellular and multicellular growth has a profound impact on our health and the economy. Many important fungal pathogens of humans, animals, and plants are dimorphic, and the ability to switch between morphological states has been associated with their virulence. Cryptococcus neoformans is a human fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised and, in some cases, immunocompetent hosts. Cryptococcus neoformans grows vegetatively as a budding yeast and switches to hyphal growth during the sexual cycle, which is important in the study of cryptococcal pathogenicity because spores resulting from sexual development are infectious propagules and can colonize the lungs of a host. In addition, sexual reproduction contributes to the genotypic variability of Cryptococcus species, which may lead to increased fitness and virulence. Despite significant advances in our understanding of the mechanisms behind the development of C. neoformans, our knowledge is still incomplete. Recent studies have led to the emergence of many intriguing questions and hypotheses. In this review, we describe and discuss the most interesting aspects of C. neoformans development and address their impact on pathogenicity.

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Section: Development Of Postmating Hyphaementioning

confidence: 99%

Section: Development Of Postmating Hyphaementioning

confidence: 99%

Profiling a killer, the development ofCryptococcus neoformans

Kozubowski

Heitman

2012

FEMS Microbiol Rev

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“…This group showed enrichment for genes with functions relating to the cytoskeleton, particularly those components that destabilize microtubules and cytoskeletal components. Cluster 8 also includes BIM1, whose gene product is known to contribute to proper microtubule organization (Staudt et al 2010).…”

Section: Gene Expression Profiling Of C Neoformans During Sexual Devmentioning

confidence: 99%

Analysis ofCryptococcus neoformansSexual Development Reveals Rewiring of the Pheromone-Response Network by a Change in Transcription Factor Identity

Kruzel¹,

Giles²,

Hull

2012

Genetics

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The fundamental mechanisms that control eukaryotic development include extensive regulation at the level of transcription. Gene regulatory networks, composed of transcription factors, their binding sites in DNA, and their target genes, are responsible for executing transcriptional programs. While divergence of these control networks drives species-specific gene expression that contributes to biological diversity, little is known about the mechanisms by which these networks evolve. To investigate how network evolution has occurred in fungi, we used a combination of microarray expression profiling, cis-element identification, and transcription-factor characterization during sexual development of the human fungal pathogen Cryptococcus neoformans. We first defined the major gene expression changes that occur over time throughout sexual development. Through subsequent bioinformatic and molecular genetic analyses, we identified and functionally characterized the C. neoformans pheromone-response element (PRE). We then discovered that transcriptional activation via the PRE requires direct binding of the high-mobility transcription factor Mat2, which we conclude functions as the elusive C. neoformans pheromone-response factor. This function of Mat2 distinguishes the mechanism of regulation through the PRE of C. neoformans from all other fungal systems studied to date and reveals species-specific adaptations of a fungal transcription factor that defies predictions on the basis of sequence alone. Overall, our findings reveal that pheromone-response network rewiring has occurred at the level of transcription factor identity, despite the strong conservation of upstream and downstream components, and serve as a model for how selection pressures act differently on signaling vs. gene regulatory components during eukaryotic evolution.

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“…Maintenance of MT structural integrity by this class of +TIP was also observed in the budding yeast Bim1 homologue of the human pathogen Cryptococcus neoformans [44]. Abnormally short and relatively unstructured MTs were observed in bim1 mutants in filaments during sexual development and during diploid filamentation, consequently changing its normal filamentous growth [44]. Similarly, MT dynamics, specifically during G1 phase of cell division, has been shown on studies of S. cerevisiae Bim1 [15].…”

Section: Discussionmentioning

confidence: 61%

“…Lack of mal3 resulted in short and often weak cytoplasmic MTs [16]. Maintenance of MT structural integrity by this class of +TIP was also observed in the budding yeast Bim1 homologue of the human pathogen Cryptococcus neoformans [44]. Abnormally short and relatively unstructured MTs were observed in bim1 mutants in filaments during sexual development and during diploid filamentation, consequently changing its normal filamentous growth [44].…”

Section: Discussionmentioning

confidence: 81%

MTB-3, a Microtubule Plus-End Tracking Protein (+TIP) of Neurospora crassa

et al. 2013

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The microtubule (MT) “plus end” constitutes the platform for the accumulation of a structurally and functionally diverse group of proteins, collectively called “MT plus-end tracking proteins” (+TIPs). +TIPs control MT dynamics and link MTs to diverse sub-cellular structures. Neurospora crassa MicroTubule Binding protein-3 (MTB-3) is the homolog of yeast EB1, a highly conserved +TIP. To address the function of MTB-3, we examined strains with mtb-3 deletions, and we tagged MTB-3 with GFP to assess its dynamic behavior. MTB-3-GFP was present as comet-like structures distributed more or less homogeneously within the hyphal cytoplasm, and moving mainly towards the apex at speeds up to 4× faster than the normal hyphal elongation rates. MTB-3-GFP comets were present in all developmental stages, but were most abundant in mature hyphae. MTB-3-GFP comets were observed moving in anterograde and retrograde direction along the hypha. Retrograde movement was also observed as originating from the apical dome. The integrity of the microtubular cytoskeleton affects the presence and dynamics of MTB-3-GFP comets, while actin does not seem to play a role. The size of MTB-3-GFP comets is affected by the absence of dynactin and conventional kinesin. We detected no obvious morphological phenotypes in Δmtb-3 mutants but there were fewer MTs in Δmtb-3, MTs were less bundled and less organized. Compared to WT, both MT polymerization and depolymerization rates were significantly decreased in Δmtb-3. In summary, the lack of MTB-3 affects overall growth and morphological phenotypes of N. crassa only slightly, but deletion of mtb-3 has strong effect on MT dynamics.

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Characterizing the role of the microtubule binding protein Bim1 in Cryptococcus neoformans

Cited by 14 publications

References 24 publications

Profiling a killer, the development ofCryptococcus neoformans

Profiling a killer, the development ofCryptococcus neoformans

Analysis ofCryptococcus neoformansSexual Development Reveals Rewiring of the Pheromone-Response Network by a Change in Transcription Factor Identity

MTB-3, a Microtubule Plus-End Tracking Protein (+TIP) of Neurospora crassa

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