Heterotrimeric G protein signaling and RGSs in Aspergillus nidulans.

Heterotrimeric G proteins (G proteins) are conserved in all eukaryotes and are crucial components sensing and relaying external cues into the cells to elicit appropriate physiological and biochemical responses. Basic units of the heterotrimeric G protein signaling system include a G protein-coupled receptor (GPCR), a G protein composed of alpha, beta, and gamma subunits, and variety of effectors. Sequential sensitization and activation of these G protein elements translates external signals into gene expression changes, resulting in appropriate cellular behaviors. Regulators of G protein signaling (RGSs) constitute a crucial element of appropriate control of the intensity and duration of G protein signaling. For the past decade, G protein signaling and its regulation have been intensively studied in a number of model and/or pathogenic fungi and outcomes of the studies provided better understanding on the upstream regulation of vegetative growth, mating, development, virulence/pathogenicity establishment, and biosynthesis of secondary metabolites in fungi. This review focuses on the characteristics of the basic upstream G protein components and RGS proteins, and their roles controlling various aspects of biological processes in the model filamentous ascomycete fungus Aspergillus nidulans. In particular, their functions in controlling hyphal proliferation, asexual spore formation, sexual fruiting, and the mycotoxin sterigmatocystin production are discussed.

[1]  Christophe d'Enfert,et al.  G-protein and cAMP-mediated signaling in aspergilli: a genomic perspective. , 2006, Fungal genetics and biology : FG & B.

[2]  H. Yim,et al.  YlaC is an extracytoplasmic function (ECF) sigma factor contributing to hydrogen peroxide resistance in Bacillus subtilis. , 2006, Journal of microbiology.

[3]  Microarray-mediated transcriptome analysis of the tributyltin (TBT)-resistant bacterium Pseudomonas aeruginosa 25W in the presence of TBT. , 2006, Journal of microbiology.

[4]  Jae-Hyuk Yu,et al.  FluG-Dependent Asexual Development in Aspergillus nidulans Occurs via Derepression , 2006, Genetics.

[5]  Jae-Hyuk Yu,et al.  The Phosducin-Like Protein PhnA Is Required for Gβγ-Mediated Signaling for Vegetative Growth, Developmental Control, and Toxin Biosynthesis in Aspergillus nidulans , 2006, Eukaryotic Cell.

[6]  S. Hill,et al.  G‐protein‐coupled receptors: past, present and future , 2006, British journal of pharmacology.

[7]  Jae-Hyuk Yu,et al.  Conservation of structure and function of the aflatoxin regulatory geneaflR fromAspergillus nidulans andA. flavus , 1996, Current Genetics.

[8]  P. V. van Haastert,et al.  The Phosducin-Like Protein PhLP1 Is Essential for Gβγ Dimer Formation in Dictyostelium discoideum , 2005, Molecular and Cellular Biology.

[9]  Jae-Hyuk Yu,et al.  Multiple Roles of a Heterotrimeric G-Protein γ-Subunit in Governing Growth and Development of Aspergillus nidulans , 2005, Genetics.

[10]  C. d’Enfert,et al.  The Heterotrimeric G-Protein GanB(α)-SfaD(β)-GpgA(γ) Is a Carbon Source Sensor Involved in Early cAMP-Dependent Germination in Aspergillus nidulans , 2005, Genetics.

[11]  Jae-Hyuk Yu,et al.  Regulation of secondary metabolism in filamentous fungi. , 2005, Annual review of phytopathology.

[12]  Jae-Hyuk Yu,et al.  The pkaB Gene Encoding the Secondary Protein Kinase A Catalytic Subunit Has a Synthetic Lethal Interaction with pkaA and Plays Overlapping and Opposite Roles in Aspergillus nidulans , 2005, Eukaryotic Cell.

[13]  H. Hamm,et al.  Phosducin‐like protein acts as a molecular chaperone for G protein βγ dimer assembly , 2005 .

[14]  D. Siderovski,et al.  G-protein signaling: back to the future , 2005, Cellular and Molecular Life Sciences.

[15]  M. Feldbrügge,et al.  Regulation of mating and pathogenic development in Ustilago maydis. , 2004, Current opinion in microbiology.

[16]  Kap-Hoon Han,et al.  The gprA and gprB genes encode putative G protein‐coupled receptors required for self‐fertilization in Aspergillus nidulans , 2004, Molecular microbiology.

[17]  Dong-Min Han,et al.  The GanB Galpha-protein negatively regulates asexual sporulation and plays a positive role in conidial germination in Aspergillus nidulans. , 2004, Genetics.

[18]  Jae-Hyuk Yu,et al.  Regulators of G‐protein signalling in Aspergillus nidulans: RgsA downregulates stress response and stimulates asexual sporulation through attenuation of GanB (Gα) signalling , 2004, Molecular microbiology.

[19]  Kap-Hoon Han,et al.  A putative G protein‐coupled receptor negatively controls sexual development in Aspergillus nidulans , 2004, Molecular microbiology.

[20]  C. D'souza,et al.  Of smuts, blasts, mildews, and blights: cAMP signaling in phytopathogenic fungi. , 2003, Annual review of phytopathology.

[21]  Jae-Hyuk Yu,et al.  Suppressor mutations bypass the requirement of fluG for asexual sporulation and sterigmatocystin production in Aspergillus nidulans. , 2003, Genetics.

[22]  Alan M. Jones,et al.  A Seven-Transmembrane RGS Protein That Modulates Plant Cell Proliferation , 2003, Science.

[23]  E. Mauceli,et al.  The genome sequence of the filamentous fungus Neurospora crassa , 2003, Nature.

[24]  P. Chidiac,et al.  Activity, regulation, and intracellular localization of RGS proteins. , 2003, Receptors & channels.

[25]  K. Shiozaki,et al.  SakA MAP kinase is involved in stress signal transduction, sexual development and spore viability in Aspergillus nidulans , 2002, Molecular microbiology.

[26]  Peter Uetz,et al.  Regulation of Stress Response Signaling by the N-terminal Dishevelled/EGL-10/Pleckstrin Domain of Sst2, a Regulator of G Protein Signaling in Saccharomyces cerevisiae * , 2002, The Journal of Biological Chemistry.

[27]  Prahlad T. Ram,et al.  G Protein Pathways , 2002, Science.

[28]  R. Prade,et al.  Osmotic stress‐coupled maintenance of polar growth in Aspergillus nidulans , 2002, Molecular microbiology.

[29]  P. Insel,et al.  RGS-PX1, a GAP for Gαs and Sorting Nexin in Vesicular Trafficking , 2001, Science.

[30]  S. Emr,et al.  Location, Location, Location: Membrane Targeting Directed by PX Domains , 2001, Science.

[31]  K. Hoe,et al.  Isolation of a Novel Gene fromSchizosaccharomyces pombe: stm1+ Encoding a Seven-transmembrane Loop Protein That May Couple with the Heterotrimeric Gα2 Protein, Gpa2* , 2001, The Journal of Biological Chemistry.

[32]  Kap-Hoon Han,et al.  The nsdD gene encodes a putative GATA‐type transcription factor necessary for sexual development of Aspergillus nidulans , 2001, Molecular microbiology.

[33]  R. Neubig,et al.  Regulator of G protein signaling proteins: novel multifunctional drug targets. , 2001, The Journal of pharmacology and experimental therapeutics.

[34]  K. Shimizu,et al.  Genetic involvement of a cAMP-dependent protein kinase in a G protein signaling pathway regulating morphological and chemical transitions in Aspergillus nidulans. , 2001, Genetics.

[35]  J. Heitman,et al.  Signal Transduction Cascades Regulating Fungal Development and Virulence , 2000, Microbiology and Molecular Biology Reviews.

[36]  T. Phillips,et al.  G‐protein signalling mediates differential production of toxic secondary metabolites , 2000, Molecular microbiology.

[37]  S. Burchett,et al.  Regulators of G Protein Signaling , 2000, Journal of neurochemistry.

[38]  Ping Wang,et al.  Identification of bdm-1, a gene involved in G protein β-subunit function and α-subunit accumulation , 2000 .

[39]  Jae-Hyuk Yu,et al.  The Aspergillus nidulans sfaD gene encodes a G protein β subunit that is required for normal growth and repression of sporulation , 1999, The EMBO journal.

[40]  J. D. de Winde,et al.  A novel regulator of G protein signalling in yeast, Rgs2, downregulates glucose‐activation of the cAMP pathway through direct inhibition of Gpa2 , 1999, The EMBO journal.

[41]  C. Gancedo,et al.  Disruption and basic functional analysis of six novel ORFs of chromosome XV from Saccharomyces cerevisiae , 1999, Yeast.

[42]  J. D. de Winde,et al.  A Saccharomyces cerevisiae G‐protein coupled receptor, Gpr1, is specifically required for glucose activation of the cAMP pathway during the transition to growth on glucose , 1999, Molecular microbiology.

[43]  C. Malbon,et al.  Physiological regulation of G protein-linked signaling. , 1999, Physiological reviews.

[44]  Jae-Hyuk Yu,et al.  Extragenic suppressors of loss-of-function mutations in the aspergillus FlbA regulator of G-protein signaling domain protein. , 1999, Genetics.

[45]  M. Bölker Sex and crime: heterotrimeric G proteins in fungal mating and pathogenesis. , 1998, Fungal genetics and biology : FG & B.

[46]  M. Ward,et al.  Yeast PKA represses Msn2p/Msn4p‐dependent gene expression to regulate growth, stress response and glycogen accumulation , 1998, The EMBO journal.

[47]  J. Hirsch,et al.  GPR1 encodes a putative G protein‐coupled receptor that associates with the Gpa2p Gα subunit and functions in a Ras‐independent pathway , 1998, The EMBO journal.

[48]  Jae-Hyuk Yu,et al.  Asexual Sporulation in Aspergillus nidulans , 1998, Microbiology and Molecular Biology Reviews.

[49]  Jae-Hyuk Yu,et al.  Dominant mutations affecting both sporulation and sterigmatocystin biosynthesis in Aspergillus nidulans , 1997, Current Genetics.

[50]  Jae-Hyuk Yu,et al.  Aspergillus sporulation and mycotoxin production both require inactivation of the FadA Gα protein‐dependent signaling pathway , 1997, The EMBO journal.

[51]  M. Yaffe,et al.  Mutational Analysis of Mdm1p Function in Nuclear and Mitochondrial Inheritance , 1997, The Journal of cell biology.

[52]  Jae-Hyuk Yu,et al.  The Aspergillus FlbA RGS domain protein antagonizes G protein signaling to block proliferation and allow development. , 1996, The EMBO journal.

[53]  T. C. Nesbitt,et al.  Twenty-five coregulated transcripts define a sterigmatocystin gene cluster in Aspergillus nidulans. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[54]  Bee-Na Lee,et al.  Overexpression of fIbA, an early regulator of Aspergillus asexual sporulation, leads to activation of brIA and premature initiation of development , 1994, Molecular microbiology.

[55]  Bee-Na Lee,et al.  The Aspergillus nidulans fluG gene is required for production of an extracellular developmental signal and is related to prokaryotic glutamine synthetase I. , 1994, Genes & development.