Fungal development and the COP9 signalosome

https://doi.org/10.1016/j.mib.2010.09.011Get rights and content

The conserved COP9 signalosome (CSN) multiprotein complex is located at the interface between cellular signaling, protein modification, life span and the development of multicellular organisms. CSN is required for light-controlled responses in filamentous fungi. This includes the circadian rhythm of Neurospora crassa or the repression of sexual development by light in Aspergillus nidulans. In contrast to plants and animals, CSN is not essential for fungal viability. Therefore fungi are suitable models to study CSN composition, activity and cellular functions and its role in light controlled development.

Introduction

The COP9 signalosome, also known as CSN, is a protein complex found in most eukaryotes from yeast to human [1, 2]. CSN was originally identified by its role in light response in plants where mutants showed a constitutively photomorphogenic/de-etiolated/fusca (COP) phenotype [3, 4]. CSN defective plants growing in the darkness display a development pattern normally seen in the light. In addition, plant CSN is required for the survival of seedlings and is involved in pathogen response [2]. In mice and flies, the absence of CSN causes embryonic death, whereas aberrant expression has been associated with tumour growth [5, 6, 7]. CSN is a platform for associated proteins and plays a central role in regulating post-translational processes as protein ubiquitination/deubiquitination, neddylation/deneddylation and phosphorylation. These properties directly affect enzymatic activities, protein stability and subcellular trafficking. Therefore CSN impinges on numerous signaling pathways affecting transcriptional regulation, DNA repair, cell cycle, cell differentiation, and development [1, 8, 9]. The archaetypal COP9 signalosome comprises the eight subunits CSN1–CSN8 and shares structural features with the lid of the 26 proteasome or translation factor eIF3. These complexes are summarized as Zomes and usually contain six PCI (proteasome/COP9/initiation factor: approximately 200 amino acids) domain proteins and two MPN (Mpr1p and Pad1p N-terminal) domain proteins. eIF3 contains four additional subunits. Additional MPN proteins include AMSH1 involved in endocytosis, or Prp8 protein functioning in RNA splicing. CSN and the lid share the highest homology, because a corresponding paralogue for each gene encoding a subunit of one complex can be assigned in the other complex. The Zomes control cellular protein levels by affecting the synthesis and the stability of proteins. Whereas eIF3 is involved in protein synthesis and the lid in protein degradation, there are various functions which are associated with CSN at the interface between protein synthesis and degradation [10].

Section snippets

CSN organisation and intrinsic function

CSN has been identified in various fungal species. It is dispensable for the growth of unicellular yeasts and of filamentous fungi [11•, 12•, 13]. This is in contrast to the slime mold Dictyostelium discoideum which requires CSN for growth [14]. Some fungi show significant differences in subunit composition in comparison to the eight-subunit CSN of higher organisms (Figure 1). Smaller versions of CSN are present in Neurospora crassa with seven [15, 16] or in the fission yeast

Fungi and the CSN paradox

The csn mutants of the fission yeast S. pombe have moderate phenotypes as delayed progression through S-phase or hypersensitivity to radiation [17, 22]. This fungus has contributed to clarify the conflicting role of CSN in vitro or in vivo on the activity of CRLs. CSN inhibits CRL in vitro, but promotes the activity of ubiquitin ligases in vivo. CSN mediated deneddylation increases in vivo the stability of specific F-box proteins by preventing autoubiquitination when substrate is absent.

CSN and light response

N. crassa csn mutants are impaired in controlling the circadian clock that adapts conidiation to the day and night rhythm and requires the frequency (FRQ) protein as essential compound of the oscillator [28]. csn mutant strains are also characterised by growth defects and reduction in aerial hyphae and conidia [15]. CSN regulates the circadian rhythm by stabilising a specific CRL complex which triggers ubiquitination of the FRQ oscillator [16]. FRQ ubiquitination requires the F-box protein FWD1

CSN and the velvet complex

A. nidulans csn mutants are blind, not only compromised in the DNA damage response [46], but also impaired in coordinated sexual development and secondary metabolism. Mutants constitutively initiate sexual development but are blocked in cleistothecia maturation at the primordia state. Red coloured hyphae reflect impaired secondary metabolism [11•] reminiscent to plant mutants which accumulate the red pigment anthocyanin [3, 38, 39, 40].

An antagonist of CSN in coordinating fungal development and

Conclusion

The identification of developmental-specific CRL ubiquitin-ligases will be one of the major tasks of the future research to unravel the role of CSN in development. Filamentous fungi are reliable model systems. Only the adaptors of cullin-1 represent approximately 70 F-box protein encoding genes in A. nidulans [50]. A first developmental CRL has been found for this fungus with the F-box protein GrrA for an SCF required during late fruit body maturation [51]. The involvement of CSN in the light

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

Research funding was provided by the Deutsche Forschungsgemeinschaft, DFG priority program SPP 1365, the Volkswagen-Stiftung, and the Fonds der Chemischen Industrie.

References (51)

  • P. Oren-Giladi et al.

    Cop9 signalosome subunit 8 (CSN8) is essential for Drosophila development

    Genes Cells

    (2008)
  • K. Lykke-Andersen et al.

    Disruption of the COP9 signalosome Csn2 subunit in mice causes deficient cell proliferation, accumulation of p53 and cyclin E, and early embryonic death

    Mol Cell Biol

    (2003)
  • S. Menon et al.

    COP9 signalosome subunit 8 is essential for peripheral T cell homeostasis and antigen receptor-induced entry into the cell cycle from quiescence

    Nat Immunol

    (2007)
  • D.A. Chamovitz

    Revisiting the COP9 signalosome as a transcriptional regulator

    EMBO Rep

    (2009)
  • J.Y. Kato et al.

    Mammalian COP9 signalosome

    Genes Cells

    (2009)
  • E. Pick et al.

    In the land of the rising sun with the COP9 signalosome and related Zomes. Symposium on the COP9 signalosome, proteasome and eIF3

    EMBO Rep

    (2009)
  • S. Busch et al.

    The COP9 signalosome is an essential regulator of development in the filamentous fungus Aspergillus nidulans

    Mol Microbiol

    (2003)
  • S. Busch et al.

    An eight-subunit COP9 signalosome with an intact JAMM motif is required for fungal fruit body formation

    Proc Natl Acad Sci U S A

    (2007)
  • K.E. Mundt et al.

    Deletion mutants in COP9/signalosome subunits in fission yeast Schizosaccharomyces pombe display distinct phenotypes

    Mol Biol Cell

    (2002)
  • D. Rosel et al.

    The COP9 signalosome regulates cell proliferation of Dictyostelium discoideum

    Eur J Cell Biol

    (2006)
  • Q. He et al.

    The COP9 signalosome regulates the Neurospora circadian clock by controlling the stability of the SCFFWD-1 complex

    Genes Dev

    (2005)
  • C. Liu et al.

    Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by both checkpoint-dependent and -independent mechanisms

    Genes Dev

    (2003)
  • V. Maytal-Kivity et al.

    COP9 signalosome components play a role in the mating pheromone response of S. cerevisiae

    EMBO Rep

    (2002)
  • G. Wu et al.

    Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase

    Mol Cell

    (2003)
  • L. Pintard et al.

    Cullin-based ubiquitin ligases: Cul3-BTB complexes join the family

    Embo J

    (2004)

    • Cited by (62)

    • Detection of quantitative trait loci underlying fruiting body and yield-related traits in Hericium erinaceus

      2022, Scientia Horticulturae

    • Structure and development of ascomata

      2021, Encyclopedia of Mycology

    • The necessity of NEDD8/Rub1 for vitality and its association with mitochondria-derived oxidative stress

      2020, Redox Biology
      Citation Excerpt :

      The proteasome lid and the CSN complexes are required for viability of multicellular organisms. Yet, unlike the high conservation of the proteasome lid across all eukaryotic phyla, the CSN shows more diversity, especially in fungal species [51–53]. For example, S. cerevisiae proteasome lid subunits can be substituted with Arabidopsis thaliana orthologs.

    • The Third International Symposium on Fungal Stress – ISFUS

      2020, Fungal Biology

    • Transcriptomic analysis of basidiocarp development in Ustilago maydis (DC) Cda.

      2017, Fungal Genetics and Biology

    • Csn5 inhibits autophagy by regulating the ubiquitination of Atg6 and Tor to mediate the pathogenicity of Magnaporthe oryzae

      2024, Cell Communication and Signaling
    View all citing articles on Scopus
    View full text
    Copyright © 2010 Elsevier Ltd. All rights reserved.