Skip to main content
SpringerLink
Log in

Characterizations and functions of regulator of G protein signaling (RGS) in fungi

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Proteins that serve as regulator of G protein signaling (RGS) primarily function as GTPase accelerators that promote GTP hydrolysis by the Gα subunits, thereby inactivating the G protein and rapidly switching off G protein-coupled signaling pathways. Since the first RGS protein was identified from the budding yeast Saccharomyces cerevisiae, more than 30 RGS and RGS-like proteins have been characterized from several model fungi, such as Aspergillus nidulans, Beauveria bassiana, Candida albicans, Fusarium verticillioides, Magnaporthe oryzae, and Metarhizium anisopliae. In this review, the partial biochemical properties and functional domains of RGS and RGS-like proteins were predicted and compared, and the roles of RGS and RGS-like proteins in different fungi were summarized. Moreover, the phylogenetic relationship among RGS and RGS-like proteins from various fungi was analyzed and discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Apanovitch DM, Slep KC, Sigler PB, Dohlman HG (1998) Sst2 is a GTPase-activating protein for Gpa1: purification and characterization of a cognate RGS-Gα protein pair in yeast. Biochem 37:4815–4822

    Article  CAS  Google Scholar 

  • Ballon DR, Flanary PL, Gladue DP, Konopka JB, Dohlman HG, Thorner J (2006) DEP-domain-mediated regulation of GPCR signaling responses. Cell 126:1079–1093

    Article  PubMed  CAS  Google Scholar 

  • Berman DM, Wilkie TM, Gilman AG (1996) GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein α subunits. Cell 86:445–452

    Article  PubMed  CAS  Google Scholar 

  • Borkovich KA, Alex LA, Yarden O, Freitag M, Turner GE, Read ND, Seiler S, Bell-Pedersen D, Paietta J, Plesofsky N, Plamann M, Goodrich-Tanrikulu M, Schulte U, Mannhaupt G, Nargang FE, Radford A, Selitrennikoff C, Galagan JE, Dunlap JC, Loros JJ, Catcheside D, Inoue H, Aramayo R, Polymenis M, Selker EU, Sachs MS, Marzluf GA, Paulsen I, Davis R, Ebbole DJ, Zelter A, Kalkman ER, O'Rourke R, Bowring F, Yeadon J, Ishii C, Suzuki K, Sakai W, Pratt R (2004) Lessons from the genome sequence of Neurospora crassa: tracing the path from genomic blueprint to multicellular organism. Microbiol Mol Biol Rev 68:1–108

    Article  PubMed  CAS  Google Scholar 

  • Burchett SA (2000) Regulators of G protein signaling: a bestiary of modular protein binding domains. J Neurochem 75:1335–1351

    Article  PubMed  CAS  Google Scholar 

  • Burchett SA, Flanary P, Aston C, Jiang L, Young KH, Uetz P, Fields S, Dohlman HG (2002) 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. J Biol Chem 277:22156–22167

    Article  PubMed  CAS  Google Scholar 

  • Chan RK, Otte CA (1982) Isolation and genetic analysis of Saccharomyces cerevisiae mutants supersensitive to G1 arrest by a factor and α factor pheromones. Mol Cell Biol 2:11–20

    PubMed  CAS  Google Scholar 

  • Chasse SA, Dohlman HG (2003) RGS proteins: G protein-coupled receptors meet their match. Assay Drug Dev Technol 1:357–364

    Article  PubMed  CAS  Google Scholar 

  • Chasse SA, Flanary P, Parnell SC, Hao N, Cha JY, Siderovski DP, Dohlman HG (2006) Genome-scale analysis reveals Sst2 as the principal regulator of mating pheromone signaling in the yeast Saccharomyces cerevisiae. Eukaryot Cell 5:330–346

    Article  PubMed  CAS  Google Scholar 

  • Chidiac P, Roy AA (2003) Activity, regulation, and intracellular localization of RGS proteins. Receptors Channels 9:135–147

    Article  PubMed  CAS  Google Scholar 

  • De Vries L, Zheng B, Fischer T, Elenko E, Farquhar MG (2000) The regulator of G protein signaling family. Annu Rev Pharmacol Toxicol 40:235–271

    Article  PubMed  Google Scholar 

  • Dignard D, Whiteway M (2006) SST2, a regulator of G-protein signaling for the Candida albicans mating response pathway. Eukaryot Cell 5:192–202

    Article  PubMed  CAS  Google Scholar 

  • Dohlman HG, Song JP, Ma DR, Courchesne WE, Thorner J (1996) Sst2, a negative regulator of pheromone signaling in the yeast Saccharomyces cerevisiae: expression, localization, and genetic interaction and physical association with Gpa1 (the G-protein α subunit). Mol Cell Biol 16:5194–5209

    PubMed  CAS  Google Scholar 

  • Druey KM, Blumer KJ, Kang VH, Kehrl JH (1996) Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family. Nature 379:742–746

    Article  PubMed  CAS  Google Scholar 

  • Ellson CD, Andrews S, Stephens LR, Hawkins PT (2002) The PX domain: a new phosphoinositide-binding module. J Cell Sci 115:1099–1105

    PubMed  CAS  Google Scholar 

  • Fang WG, Pei Y, Bidochka MJ (2007) A regulator of a G protein signalling (RGS) gene, cag8, from the insect-pathogenic fungus Metarhizium anisopliae is involved in conidiation, virulence and hydrophobin synthesis. Microbiology 153:1017–1025

    Article  PubMed  CAS  Google Scholar 

  • Fang WG, Scully LR, Zhang L, Pei Y, Bidochka MJ (2008) Implication of a regulator of G protein signalling (BbRGS1) in conidiation and conidial thermotolerance of the insect pathogenic fungus Beauveria bassiana. FEMS Microbiol Lett 279:146–156

    Article  PubMed  CAS  Google Scholar 

  • Fisk HA, Yaffe MP (1997) Mutational analysis of Mdm1p function in nuclear and mitochondrial inheritance. J Cell Biol 138:485–494

    Article  PubMed  CAS  Google Scholar 

  • Fujita A, Lord M, Hiroko T, Hiroko F, Chen T, Oka C, Misumi Y, Chant J (2004) Rax1, a protein required for the establishment of the bipolar budding pattern in yeast. Gene 327:161–169

    Article  PubMed  CAS  Google Scholar 

  • Galagan JE, Calvo SE, Borkovich KA, Selker EU, Read ND, Jaffe D, FitzHugh W, Ma LJ, Smirnov S, Purcell S, Rehman B, Elkins T, Engels R, Wang S, Nielsen CB, Butler J, Endrizzi M, Qui D, Ianakiev P, Bell-Pedersen D, Nelson MA, Werner-Washburne M, Selitrennikoff CP, Kinsey JA, Braun EL, Zelter A, Schulte U, Kothe GO, Jedd G, Mewes W, Staben C, Marcotte E, Greenberg D, Roy A, Foley K, Naylor J, Stange-Thomann N, Barrett R, Gnerre S, Kamal M, Kamvysselis M, Mauceli E, Bielke C, Rudd S, Frishman D, Krystofova S, Rasmussen C, Metzenberg RL, Perkins DD, Kroken S, Cogoni C, Macino G, Catcheside D, Li W, Pratt RJ, Osmani SA, DeSouza CP, Glass L, Orbach MJ, Berglund JA, Voelker R, Yarden O, Plamann M, Seiler S, Dunlap J, Radford A, Aramayo R, Natvig DO, Alex LA, Mannhaupt G, Ebbole DJ, Freitag M, Paulsen I, Sachs MS, Lander ES, Nusbaum C, Birren B (2003) The genome sequence of the filamentous fungus Neurospora crassa. Nature 422:859–868

    Article  PubMed  CAS  Google Scholar 

  • Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR, Appel RD, Barioch A (2005) Protein identification and analysis tools on the ExPASy server. In: Walker JM, Totowa NJ (eds) The proteomics protocols handbook. Humana Press Inc, New Jersey, pp 571–607

    Chapter  Google Scholar 

  • Guan KL, Han M (1999) A G-protein signaling network mediated by an RGS protein. Genes Dev 13:1763–1767

    Article  PubMed  CAS  Google Scholar 

  • Han KH, Seo JA, Yu JH (2004) Regulators of G-protein signalling in Aspergillus nidulans: RgsA downregulates stress response and stimulates asexual sporulation through attenuation of GanB (Gα) signalling. Mol Microbiol 53:529–540

    Article  PubMed  CAS  Google Scholar 

  • Hepler JR, Berman DM, Gilman AG, Kozasa T (1997) RGS4 and GAIP are GTPase-activating proteins for Gqα and block activation of phospholipase Cβ by γ-thio-GTP-Gqα. Proc Natl Acad Sci U S A 94:428–432

    Article  PubMed  CAS  Google Scholar 

  • Hosomi A, Kawanishi YY, Tanaka N, Takegawa K (2008) PXA domain-containing protein Pxa1 is required for normal vacuole function and morphology in Schizosaccharomyces pombe. Biosci Biotechnol Biochem 72:548–556

    Article  PubMed  CAS  Google Scholar 

  • Huang LJ, Durick K, Weiner JA, Chun J, Taylor SS (1997) D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain. Proc Natl Acad Sci U S A 94:11184–11189

    Article  PubMed  CAS  Google Scholar 

  • Hunt TW, Fields TA, Casey PJ, Peralta EG (1996) RGS10 is a selective activator of Gαi GTPase activity. Nature 383:175–177

    Article  PubMed  CAS  Google Scholar 

  • Lafon A, Seo JA, Han KH, Yu JH, d’Enfert C (2005) The heterotrimeric G-protein GanB(α)-SfaD(β)-GpgA(γ) is a carbon source sensor involved in early cAMP-dependent germination in Aspergillus nidulans. Genetics 171:71–80

    Article  PubMed  CAS  Google Scholar 

  • Lafuente MJ, Gancedo C (1999) Disruption and basic functional analysis of six novel ORFs of chromosome XV from Saccharomyces cerevisiae. Yeast 15:935–943

    Article  PubMed  CAS  Google Scholar 

  • Lee BN, Adams TH (1994) Overexpression of flbA, an early regulator of Aspergillus asexual sporulation, leads to activation of brlA and premature initiation of development. Mol Microbiol 14:323–334

    Article  PubMed  CAS  Google Scholar 

  • Lengeler KB, Davidson RC, D'souza C, Harashima T, Shen WC, Wang P, Pan X, Waugh M, Heitman J (2000) Signal transduction cascades regulating fungal development and virulence. Microbiol Mol Biol Rev 64:746–785

    Article  PubMed  CAS  Google Scholar 

  • Li L, Wright SJ, Krystofova S, Park G, Borkovich KA (2007) Heterotrimeric G protein signaling in filamentous fungi. Annu Rev Microbiol 61:423–452

    Article  PubMed  CAS  Google Scholar 

  • Liu H, Suresh A, Willard FS, Siderovski DP, Lu S, Naqvi NI (2007) Rgs1 regulates multiple Gα subunits in Magnaporthe pathogenesis, asexual growth and thigmotropism. EMBO J 26:690–700

    Article  PubMed  CAS  Google Scholar 

  • Logothetis DE, Kurachi Y, Galper J, Neer EJ, Clapham DE (1987) The βγ subunits of GTP-binding proteins activate the muscarinic K+ channel in heart. Nature 325:321–326

    Article  PubMed  CAS  Google Scholar 

  • Longenecker KL, Lewis ME, Chikumi H, Gutkind JS, Derewenda ZS (2001) Structure of the RGS-like domain from PDZ-RhoGEF: linking heterotrimeric G protein-coupled signaling to Rho GTPases. Structure 9:559–569

    Article  PubMed  CAS  Google Scholar 

  • McConnell SJ, Stewart LC, Talin A, Yaffe MP (1990) Temperature-sensitive yeast mutants defective in mitochondrial inheritance. J Cell Biol 111:967–976

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee M, Kim JE, Park YS, Kolomiets MV, Shim WB (2011) Regulators of G-protein signalling in Fusarium verticillioides mediate differential host–pathogen responses on nonviable versus viable maize kernels. Mol Plant Pathol 12:479–491

    Article  PubMed  CAS  Google Scholar 

  • Neves SR, Ram PT, Iyengar R (2002) G protein pathways. Science 296:1636–1639

    Article  PubMed  CAS  Google Scholar 

  • Park AR, Cho AR, Seo JA, Min K, Son H, Lee J, Choi GJ, Kim JC, Lee YW (2012) Functional analyses of regulators of G protein signaling in Gibberella zeae. Fungal Genet Biol 49:511–520

    Article  PubMed  CAS  Google Scholar 

  • Popov S, Yu K, Kozasa T, Wilkie TM (1997) The regulators of G protein signaling (RGS) domains of RGS4, RGS10, and GAIP retain GTPase activating protein activity in vitro. Proc Natl Acad Sci U S A 94:7216–7220

    Article  PubMed  CAS  Google Scholar 

  • Porter MY, Koelle MR (2009) Insights into RGS protein function from studies in Caenorhabditis elegans. Prog Mol Biol Transl Sci 86:15–47

    Article  PubMed  CAS  Google Scholar 

  • Sato TK, Overduin M, Emr SD (2001) Location, location, location: membrane targeting directed by PX domains. Science 294:1881–1885

    Article  PubMed  CAS  Google Scholar 

  • Seet LF, Hong W (2006) The Phox (PX) domain proteins and membrane traffic. Biochim Biophys Acta 1761:878–896

    Article  PubMed  CAS  Google Scholar 

  • Shen G, Wang YL, Whittington A, Li L, Wang P (2008) The RGS protein Crg2 regulates pheromone and cyclic AMP signaling in Cryptococcus neoformans. Eukaryot Cell 7:1540–1548

    Article  PubMed  CAS  Google Scholar 

  • Siderovski DP, Willard FS (2005) The GAPs, GEFs, and GDIs of heterotrimeric G-protein α subunits. Int J Biol Sci 1:51–66

    Article  PubMed  CAS  Google Scholar 

  • Soundararajan M, Willard FS, Kimple AJ, Turnbull AP, Ball LJ, Schoch GA, Gileadi C, Fedorov OY, Dowler EF, Higman VA, Hutsell SQ, Sundström M, Doyle DA, Siderovski DP (2008) Structural diversity in the RGS domain and its interaction with heterotrimeric G protein α-subunits. Proc Natl Acad Sci U S A 105:6457–6462

    Article  PubMed  CAS  Google Scholar 

  • Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739

    Article  PubMed  CAS  Google Scholar 

  • Tesmer JJ, Berman DM, Gilman AG, Sprang SR (1997) Structure of RGS4 bound to AlF4 −-activated Giα1: stabilization of the transition state for GTP hydrolysis. Cell 89:251–261

    Article  PubMed  CAS  Google Scholar 

  • Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The Clustal_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acid Res 25:4876–4882

    Article  PubMed  CAS  Google Scholar 

  • Versele M, de Winde JH, Thevelein JM (1999) A novel regulator of G protein signalling in yeast, Rgs2, downregulates glucose-activation of the cAMP pathway through direct inhibition of Gpa2. EMBO J 18:5577–5591

    Article  PubMed  CAS  Google Scholar 

  • Wang P, Cutler J, King J, Palmer D (2004) Mutation of the regulator of G protein signaling Crg1 increases virulence in Cryptococcus neoformans. Eukaryot Cell 3:1028–1035

    Article  PubMed  CAS  Google Scholar 

  • Xue C, Hsueh YP, Chen L, Heitman J (2008) The RGS protein Crg2 regulates both pheromone and cAMP signalling in Cryptococcus neoformans. Mol Microbiol 70:379–395

    Article  PubMed  CAS  Google Scholar 

  • Yang JK, Wang L, Ji XL, Feng Y, Li XM, Zou CG, Xu JP, Ren Y, Mi QL, Wu JL, Liu SQ, Liu Y, Huang XW, Wang HY, Niu XM, Li J, Liang LM, Luo YL, Ji KF, Zhou W, Yu ZF, Li GH, Liu YJ, Li L, Qiao M, Feng L, Zhang KQ (2011) Genomic and proteomic analyses of the fungus Arthrobotrys oligospora provide insights into nematode-trap formation. PLoS Pathog 7:e1002179

    Article  PubMed  CAS  Google Scholar 

  • Yi TM, Kitano H, Simon MI (2003) A quantitative characterization of the yeast heterotrimeric G protein cycle. Proc Natl Acad Sci U S A 100:10764–10769

    Article  PubMed  CAS  Google Scholar 

  • Yu JH (2006) Heterotrimeric G protein signaling and RGSs in Aspergillus nidulans. J Microbiol 44:145–154

    PubMed  CAS  Google Scholar 

  • Yu JH, Keller N (2005) Regulation of secondary metabolism in filamentous fungi. Annu Rev Phytopathol 43:437–458

    Article  PubMed  CAS  Google Scholar 

  • Yu JW, Lemmon MA (2001) All phox homology (PX) domains from Saccharomyces cerevisiae specifically recognize phosphatidylinositol 3-phosphate. J Biol Chem 276:44179–44184

    Article  PubMed  CAS  Google Scholar 

  • Zdobnov EM, Apweiler R (2001) InterProScan—an integration platform for the signature-recognition methods in InterPro. Bioinformatics 17:847–848

    Article  PubMed  CAS  Google Scholar 

  • Zhang H, Tang W, Liu K, Huang Q, Zhang X, Yan X, Chen Y, Wang J, Qi Z, Wang Z, Zheng X, Wang P, Zhang Z (2011) Eight RGS and RGS-like proteins orchestrate growth, differentiation, and pathogenicity of Magnaporthe oryzae. PLoS Pathog 7:e1002450

    Article  PubMed  CAS  Google Scholar 

  • Zheng B, Ma YC, Ostrom RS, Lavoie C, Gill GN, Insel PA, Huang XY, Farquhar MG (2001) RGS-PX1, a GAP for GαS and sorting nexin in vesicular trafficking. Science 294:1939–1942

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to Prof. Jianping Xu of the Department of Biology, McMaster University, for the valuable comments and critical discussions. The research described here is jointly supported by the National Basic Research Program of China (2013CB127500), the National Natural Science Foundation of China (approved nos. 31272093 and 30960229), the Department of Science and Technology of Yunnan Province (2009CI052), the West Light Foundation of the Chinese Academy of Sciences (to Jinkui Yang), and the China National Tobacco Corporation (110201002023). We also thank the anonymous reviewers of the manuscript for their valuable comments and suggestions.

Author information

Authors and Affiliations

  1. Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory of Microbial Diversity in Southwest China, Ministry of Education, Yunnan University, Kunming, 650091, People’s Republic of China

    Yunchuan Wang, Zongyi Geng, Dewei Jiang, Fangfang Long, Yong Zhao, Hao Su, Ke-Qin Zhang & Jinkui Yang

Authors
  1. Yunchuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zongyi Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dewei Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fangfang Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yong Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hao Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ke-Qin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jinkui Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ke-Qin Zhang or Jinkui Yang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, Y., Geng, Z., Jiang, D. et al. Characterizations and functions of regulator of G protein signaling (RGS) in fungi. Appl Microbiol Biotechnol 97, 7977–7987 (2013). https://doi.org/10.1007/s00253-013-5133-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-013-5133-1

Keywords

Search

Navigation