Journal ArticleDOI
Impairment of calcineurin function in Neurospora crassa reveals its essential role in hyphal growth, morphology and maintenance of the apical Ca2+ gradient
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TLDR
In vitro inhibition of N. crassa calcineurin by the complex of cyclosporin A (CsA) and cyclophilin20, and increased sensitivity of the induced transformants to the calcineuin-specific drugs CsA and FK506 imply that the drugs act in N.crassa, as in T-cells and Saccharomyces cerevisiae, by inactivating calcineURin.Abstract:
The function of Neurospora crassa calcineurin was investigated in N. crassa strains transformed with a construct that provides for the inducible expression of antisense RNA for the catalytic subunit of calcineurin (cna-1). Induction of antisense RNA expression was associated with reduced levels of cna-1 mRNA and of immunodetectable CNA1 protein and decreased calcineurin enzyme activity, indicating that a conditional reduction of the target function had been achieved in antisense transformants with multiple construct integrations. Induction conditions caused growth arrest which indicated that the cna-1 gene is essential for growth of N. crassa. Growth arrest was preceded by an increase in hyphal branching, changes in hyphal morphology and concomitant loss of the distinctive tip-high Ca2+ gradient typical for growing wild-type hyphae. This demonstrates a novel and specific role for calcineurin in the precise regulation of apical growth, a common form of cellular proliferation. In vitro inhibition of N. crassa calcineurin by the complex of cyclosporin A (CsA) and cyclophilin20, and increased sensitivity of the induced transformants to the calcineurin-specific drugs CsA and FK506 imply that the drugs act in N. crassa, as in T-cells and Saccharomyces cerevisiae, by inactivating calcineurin. The finding that exposure of growing wild-type mycelium to these drugs leads to a phenotype very similar to that of the cna-1 antisense mutants is consistent with this idea.read more
Citations
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Journal ArticleDOI
Calcineurin : form and function
Frank Rusnak,Pamela Mertz +1 more
TL;DR: This review provides a comprehensive examination of the biological roles of calcineurin and reviews aspects related to its structure and catalytic mechanism.
Journal ArticleDOI
Lessons from the Genome Sequence of Neurospora crassa: Tracing the Path from Genomic Blueprint to Multicellular Organism
Katherine A. Borkovich,Lisa A. Alex,Oded Yarden,Michael Freitag,Gloria E. Turner,Nick D. Read,Stephan Seiler,Deborah Bell-Pedersen,John V. Paietta,Nora Plesofsky,Michael Plamann,Marta Goodrich-Tanrikulu,Ulrich Schulte,Gertrud Mannhaupt,Frank E. Nargang,Alan Radford,Claude P. Selitrennikoff,James E. Galagan,Jay C. Dunlap,Jennifer J. Loros,David E. A. Catcheside,Hirokazu Inoue,Rodolfo Aramayo,Michael Polymenis,Eric U. Selker,Matthew S. Sachs,George A. Marzluf,Ian T. Paulsen,Rowland H. Davis,Daniel J. Ebbole,Alex Zelter,Eric R. Kalkman,Rebecca O’Rourke,Frederick J. Bowring,Jane Yeadon,Chizu Ishii,Keiichiro Suzuki,Wataru Sakai,Robert Pratt +38 more
TL;DR: An analysis of over 1,100 of the ∼10,000 predicted proteins encoded by the genome sequence of the filamentous fungus Neurospora crassa reveals potential new targets for antifungals as well as loci implicated in human and plant physiology and disease.
Journal ArticleDOI
Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence
TL;DR: Calcineurin was found to be necessary for the virulence of C. albicans in a mice model of infection, thus making calcineur in an important element for adequate adaptation to the conditions of the host environment.
Book ChapterDOI
Calcineurin: from structure to function.
TL;DR: The use of the calcineurin inhibitors—namely, FK506 and CsA, together with yeast genetics and the overexpression of calcineURin by transgenic mice, has established the critical roles of calcinesurin in the regulation of many cellular processes that are induced by changes in the concentration of intracellular Ca 2+ in response to external signals.
Journal ArticleDOI
Calcineurin Controls Growth, Morphology, and Pathogenicity in Aspergillus fumigatus
William J. Steinbach,Robert A. Cramer,B. Zachary Perfect,Yohannes G. Asfaw,Theodor C. Sauer,Laura K. Najvar,William R. Kirkpatrick,Thomas F. Patterson,Daniel K. Benjamin,Joseph Heitman,John R. Perfect +10 more
TL;DR: The results support the clinical observation that substantially decreasing fungal growth can prevent disease establishment and decrease mortality and reveal that calcineurin appears to play a globally conserved role in the virulence of several pathogenic fungi and yet plays specialized roles in each and can be an excellent target for therapeutic intervention.
References
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Journal ArticleDOI
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Jun Liu,Jesse D. Farmer,Willam S. Lane,Jeffrey S. Friedman,Irving L. Weissman,Stuart L. Schreiber +5 more
TL;DR: The results suggest that calcineurin is involved in a common step associated with T cell receptor and IgE receptor signaling pathways and that cyclophilin and FKBP mediate the actions of CsA and Fk506 by forming drug-dependent complexes with and altering the activity of calcineURin-calmodulin.
Journal ArticleDOI
The mechanism of action of cyclosporin A and FK506
TL;DR: Recent findings that indicate CsA and FK506 operate as prodrugs are reviewed: they bind endogenous intracellular receptors, the immunophilins, and the resulting complex targets the protein phosphatase, calcineurin, to exert the immunosuppressive effect.
Book ChapterDOI
[4] Genetic and microbiological research techniques for Neurospora crassa
TL;DR: This chapter describes the microbiological and genetic handling of Neurospora crassa and reviews the biochemical methods of neurospora, a member of the fungal class Ascomycetes.
Journal ArticleDOI
Signal transmission between the plasma membrane and nucleus of t lymphocytes
TL;DR: The role of NF-Kl3 and AP-l in T Cell Activation and the role of Calcineurin in Other Cells and Species are discussed.
Journal ArticleDOI
Premeiotic Instability of Repeated Sequences in Neurospora crassa
TL;DR: Premeiotic intrachromosomal recombination deletes tandem repeats at high frequency in both homothallic and heterothallic filamentous ascomycetes, which potentially stabilizes the gross organization of the genome.