Phosphorylation of Calcineurin at a Novel Serine-Proline Rich Region Orchestrates Hyphal Growth and Virulence in Aspergillus fumigatus

PLoS Pathogens

Volumn 9, Issue 8, 2013, Pages

  Juvvadi, Praveen R ^a   Gehrke, Christopher ^a   Fortwendel, Jarrod R ^a,d   Lamoth, Frédéric ^a   Soderblom, Erik J ^b   Cook, Erik C ^c   Hast, Michael A ^a   Asfaw, Yohannes G ^a   Moseley, M Arthur ^b   Creamer, Trevor P ^c   Steinbach, William J ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b DUKE UNIVERSITY   (United States)

^c UNIVERSITY OF KENTUCKY   (United States)

^d UNIVERSITY OF SOUTH ALABAMA COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALCINEURIN; CASEIN KINASE I; GLYCOGEN SYNTHASE KINASE 3BETA; PROLINE; SERINE; TACROLIMUS; ANTIFUNGAL AGENT; CALCINEURIN INHIBITOR; FUNGAL PROTEIN;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; ASPERGILLUS FUMIGATUS; CIRCULAR DICHROISM; CONTROLLED STUDY; ELECTROSPRAY MASS SPECTROMETRY; FLUORESCENCE MICROSCOPY; FUNGAL VIRULENCE; FUNGUS GROWTH; GENE MUTATION; HISTOPATHOLOGY; LIQUID CHROMATOGRAPHY; MALE; MOLECULAR CLONING; MOLECULAR MODEL; MOUSE; MUTATIONAL ANALYSIS; NONHUMAN; PHYLOGENY; PROTEIN INTERACTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PURIFICATION; SEQUENCE ALIGNMENT; SURVIVAL; TANDEM MASS SPECTROMETRY; WESTERN BLOTTING; ANIMAL; ANTAGONISTS AND INHIBITORS; ASPERGILLOSIS; BIOLOGICAL MODEL; CHEMISTRY; ENZYMOLOGY; FUNGUS HYPHAE; GENETICS; HUMAN; IMMUNOLOGY; METABOLISM; PHOSPHORYLATION; PROTEIN MOTIF; PROTEIN TERTIARY STRUCTURE;

AMINO ACID MOTIFS; ANIMALS; ANTIFUNGAL AGENTS; ASPERGILLOSIS; ASPERGILLUS FUMIGATUS; CALCINEURIN; CALCINEURIN INHIBITORS; FUNGAL PROTEINS; HUMANS; HYPHAE; MALE; MICE; MODELS, BIOLOGICAL; PHOSPHORYLATION; PROTEIN STRUCTURE, TERTIARY;

EID: 84883395367     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003564     Document Type: Article

References (52)

1. Kontoyiannis DP, Marr KA, Park BJ, Alexander BD, Anaissie EJ, et al. (2010) Prospective Surveillance for Invasive Fungal Infections in Hematopoietic Stem Cell Transplant Recipients, 2001-2006: Overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clinical Infectious Diseases 50: 1091-1100.
2. Steinbach WJ, Marr KA, Anaissie EJ, Azie N, Quan S-P, et al. (2012) Clinical epidemiology of 960 patients with invasive aspergillosis from the PATH Alliance registry. Journal of Infection 65: 453-464.
3. Steinbach WJ, Cramer RA, Perfect BZ, Asfaw YG, Sauer TC, et al. (2006) Calcineurin Controls Growth, Morphology, and Pathogenicity in Aspergillus fumigatus. Eukaryotic Cell 5: 1091-1103.
4. Steinbach WJ, Reedy JL, Cramer RA, Perfect JR, Heitman J, (2007) Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. Nat Rev Micro 5: 418-430.
5. Steinbach WJ, Schell WA, Blankenship JR, Onyewu C, Heitman J, et al. (2004) In Vitro Interactions between Antifungals and Immunosuppressants against Aspergillus fumigatus. Antimicrobial Agents and Chemotherapy 48: 1664-1669.
6. Klee CB, Crouch TH, Krinks MH, (1979) Calcineurin: a calcium- and calmodulin-binding protein of the nervous system. Proceedings of the National Academy of Sciences 76: 6270-6273.
7. Rusnak F, Mertz P, (2000) Calcineurin: Form and Function. Physiological Reviews 80: 1483-1521.
8. Clipstone NA, Crabtree GR, (1992) Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature 357: 695-697.
9. Molkentin JD, Lu J-R, Antos CL, Markham B, Richardson J, et al. (1998) A Calcineurin-Dependent Transcriptional Pathway for Cardiac Hypertrophy. Cell 93: 215-228.
10. Yakel JL, (1997) Calcineurin regulation of synaptic function: from ion channels to transmitter release and gene transcription. Trends in Pharmacological Sciences 18: 124-134.
11. Wang H-G, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, et al. (1999) Ca2+-Induced Apoptosis Through Calcineurin Dephosphorylation of BAD. Science 284: 339-343.
12. Ariño J, Ramos J, Sychrová H, (2010) Alkali Metal Cation Transport and Homeostasis in Yeasts. Microbiology and Molecular Biology Reviews 74: 95-120.
13. Levin DE, (2011) Regulation of Cell Wall Biogenesis in Saccharomyces cerevisiae: The Cell Wall Integrity Signaling Pathway. Genetics 189: 1145-1175.
14. Withee JL, Mulholland J, Jeng R, Cyert MS, (1997) An essential role of the yeast pheromone-induced Ca2+ signal is to activate calcineurin. Molecular Biology of the Cell 8: 263-277.
15. Cyert MS, (2003) Calcineurin signaling in Saccharomyces cerevisiae: how yeast go crazy in response to stress. Biochemical and Biophysical Research Communications 311: 1143-1150.
16. Lu Y, Sugiura R, Yada T, Cheng H, Sio SO, et al. (2002) Calcineurin is implicated in the regulation of the septation initiation network in fission yeast. Genes to Cells 7: 1009-1019.
17. Miyatake M, Kuno T, Kita A, Katsura K, Takegawa K, et al. (2007) Valproic Acid Affects Membrane Trafficking and Cell-Wall Integrity in Fission Yeast. Genetics 175: 1695-1705.
18. Fox DS, Heitman J, (2002) Good fungi gone bad: The corruption of calcineurin. BioEssays 24: 894-903.
19. Brown SM, Campbell LT, Lodge JK, (2007) Cryptococcus neoformans, a fungus under stress. Current Opinion in Microbiology 10: 320-325.
20. Reedy JL, Filler SG, Heitman J, (2010) Elucidating the Candida albicans calcineurin signaling cascade controlling stress response and virulence. Fungal Genetics and Biology 47: 107-116.
21. Kahl CR, Means AR, (2003) Regulation of Cell Cycle Progression by Calcium/Calmodulin-Dependent Pathways. Endocrine Reviews 24: 719-736.
22. Juvvadi PR, Kuroki Y, Arioka M, Nakajima H, Kitamoto K, (2003) Functional analysis of the calcineurin-encoding gene cnaA from Aspergillus oryzae: evidence for its putative role in stress adaptation. Archives of Microbiology 179: 416-422.
23. Kothe GO, Free SJ, (1998) Calcineurin Subunit B Is Required for Normal Vegetative Growth inNeurospora crassa. Fungal Genetics and Biology 23: 248-258.
24. Harel A, Bercovich S, Yarden O, (2006) Calcineurin Is Required for Sclerotial Development and Pathogenicity of Sclerotinia sclerotiorum in an Oxalic Acid-Independent Manner. Molecular Plant-Microbe Interactions 19: 682-693.
25. Choi JH, Kim Yang Seon, Lee Yong-Hwan, (2009) Functional Analysis of MCNA, a Gene Encoding a Catalytic Subunit of Calcineurin, in the Rice Blast Fungus Magnaporthe oryzae. J Microbiol Biotechnol 19: 11-16.
26. Li H, Rao A, Hogan PG, (2011) Interaction of calcineurin with substrates and targeting proteins. Trends in Cell Biology 21: 91-103.
27. King MM, Huang CY, (1984) The calmodulin-dependent activation and deactivation of the phosphoprotein phosphatase, calcineurin, and the effect of nucleotides, pyrophosphate, and divalent metal ions. Identification of calcineurin as a Zn and Fe metalloenzyme. Journal of Biological Chemistry 259: 8847-8856.
28. Singh TJ, Wang JH, (1987) Phosphorylation of calcineurin by glycogen synthase (casein) kinase-1. Biochemistry and Cell Biology 65: 917-921.
29. Hashimoto Y, King MM, Soderling TR, (1988) Regulatory interactions of calmodulin-binding proteins: phosphorylation of calcineurin by autophosphorylated Ca2+/calmodulin-dependent protein kinase II. Proceedings of the National Academy of Sciences 85: 7001-7005.
30. Martensen TM, Martin BM, Kincaid RL, (1989) Identification of the site on calcineurin phosphorylated by calcium/CaM-dependent kinase II: modification of the CaM-binding domain. Biochemistry 28: 9243-9247.
31. Hashimoto Y, Soderling TR, (1989) Regulation of calcineurin by phosphorylation. Identification of the regulatory site phosphorylated by Ca2+/calmodulin-dependent protein kinase II and protein kinase C. Journal of Biological Chemistry 264: 16524-16529.
32. Calalb MB, Kincaid RL, Soderling TR, (1990) Phosphorylation of calcineurin: Effect on calmodulin binding. Biochemical and Biophysical Research Communications 172: 551-556.
33. Kume K, Koyano T, Kanai M, Toda T, Hirata D, (2011) Calcineurin ensures a link between the DNA replication checkpoint and microtubule-dependent polarized growth. Nat Cell Biol 13: 234-242.
34. Ferreira MEdS, Heinekamp T, Härtl A, Brakhage AA, Semighini CP, et al. (2007) Functional characterization of the Aspergillus fumigatus calcineurin. Fungal Genetics and Biology 44: 219-230.
35. Juvvadi PR, Fortwendel JR, Pinchai N, Perfect BZ, Heitman J, et al. (2008) Calcineurin Localizes to the Hyphal Septum in Aspergillus fumigatus: Implications for Septum Formation and Conidiophore Development. Eukaryotic Cell 7: 1606-1610.
36. Juvvadi PR, Fortwendel JR, Rogg LE, Burns KA, Randell SH, et al. (2011) Localization and activity of the calcineurin catalytic and regulatory subunit complex at the septum is essential for hyphal elongation and proper septation in Aspergillus fumigatus. Molecular Microbiology 82: 1235-1259.
37. Fortwendel JR, Juvvadi PR, Perfect BZ, Rogg LE, Perfect JR, et al. (2010) Transcriptional Regulation of Chitin Synthases by Calcineurin Controls Paradoxical Growth of Aspergillus fumigatus in Response to Caspofungin. Antimicrobial Agents and Chemotherapy 54: 1555-1563.
38. Li H, Zhang L, Rao A, Harrison SC, Hogan PG, (2007) Structure of Calcineurin in Complex with PVIVIT Peptide: Portrait of a Low-affinity Signalling Interaction. Journal of Molecular Biology 369: 1296-1306.
39. Kay BK, Williamson MP, Sudol M, (2000) The importance of being proline: the interaction of proline-rich motifs in signaling proteins with their cognate domains. The FASEB Journal 14: 231-241.
40. Lu KP, Liou Y-C, Zhou XZ, (2002) Pinning down proline-directed phosphorylation signaling. Trends in Cell Biology 12: 164-172.
41. Cohen P, Frame S, (2001) The renaissance of GSK3. Nat Rev Mol Cell Biol 2: 769-776.
42. Berzal S, Alique M, Ruiz-Ortega M, Egido J, Ortiz A, et al. (2012) GSK3, Snail, and Adhesion Molecule Regulation by Cyclosporine A in Renal Tubular Cells. Toxicological Sciences 127: 425-437.
43. Rumi-Masante J, Rusinga FI, Lester TE, Dunlap TB, Williams TD, et al. (2012) Structural Basis for Activation of Calcineurin by Calmodulin. Journal of Molecular Biology 415: 307-317.
44. Fortwendel JR, Juvvadi PR, Pinchai N, Perfect BZ, Alspaugh JA, et al. (2009) Differential Effects of Inhibiting Chitin and 1,3-β-d-Glucan Synthesis in Ras and Calcineurin Mutants of Aspergillus fumigatus. Antimicrobial Agents and Chemotherapy 53: 476-482.
45. Roy J, Li H, Hogan PG, Cyert MS, (2007) A Conserved Docking Site Modulates Substrate Affinity for Calcineurin, Signaling Output, and In Vivo Function. Molecular Cell 25: 889-901.
46. Ye Q, Wang H, Zheng J, Wei Q, Jia Z, (2008) The complex structure of calmodulin bound to a calcineurin peptide. Proteins: Structure, Function, and Bioinformatics 73: 19-27.
47. Chen S, Song Y, Cao J, Wang G, Wei H, et al. (2010) Localization and function of calmodulin in live-cells of Aspergillus nidulans. Fungal Genetics and Biology 47: 268-278.
48. Jiang B, Cyert MS, (1999) Identification of a Novel Region Critical for Calcineurin Function in Vivo and in Vitro. Journal of Biological Chemistry 274: 18543-18551.
49. Ho S, Clipstone N, Timmermann L, Northrop J, Graef I, et al. (1996) The Mechanism of Action of Cyclosporin A and FK506. Clinical Immunology and Immunopathology 80: S40-S45.
50. Hilioti Z, Gallagher DA, Low-Nam ST, Ramaswamy P, Gajer P, et al. (2004) GSK-3 kinases enhance calcineurin signaling by phosphorylation of RCNs. Genes & Development 18: 35-47.
51. Juvvadi PR, Belina D, Soderblom EJ, Moseley MA, Steinbach WJ, (2013) Filamentous fungal-specific septin AspE is phosphorylated in vivo and interacts with actin, tubulin and other septins in the human pathogen Aspergillus fumigatus. Biochemical and Biophysical Research Communications 431: 547-553.
52. Steinbach WJ, Benjamin DK Jr, Trasi SA, Miller JL, Schell WA, et al. (2004) Value of an inhalational model of invasive aspergillosis. Medical Mycology 42: 417-425.