Accumulation of specific sterol precursors targets a MAP kinase cascade mediating cell–cell recognition and fusion.
Open accessAbstract
Sterols are vital components of eukaryotic cell membranes. Defects in sterol biosynthesis, which result in the accumulation of precursor molecules, are commonly associated with cellular disorders and disease. However, the effects of these sterol precursors on the metabolism, signaling, and behavior of cells are only poorly understood. In this study, we show that the accumulation of only ergosterol precursors with a conjugated double bond in their aliphatic side chain specifically disrupts cell-cell communication and fusion in the fungus Neurospora crassa Genetically identical germinating spores of this fungus undergo cell-cell fusion, thereby forming a highly interconnected supracellular network during colony initiation. Before fusion, the cells use an unusual signaling mechanism that involves the coordinated and alternating switching between signal sending and receiving states of the two fusion partners. Accumulation of only ergosterol precursors with a conjugated double bond in their aliphatic side chain disrupts this coordinated cell-cell communication and suppresses cell fusion. These specific sterol precursors target a single ERK-like mitogen-activated protein (MAP) kinase (MAK-1)-signaling cascade, whereas a second MAP kinase pathway (MAK-2), which is also involved in cell fusion, is unaffected. These observations indicate that a minor specific change in sterol structure can exert a strong detrimental effect on a key signaling pathway of the cell, resulting in the absence of cell fusion.
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In N. crassa, ergosterol was detected in Δerg3 but not in Δerg2, Δerg4 or Δerg5 mutants.
“Similar as wild type, ergosterol was easily detected in Δerg3 strain, possibly due to the present of a second copy of erg3 (Weichert et al., 2016). While in the Δerg2, Δerg4 and Δerg5 strains, no ergosterol were detected (Figure 4B).”
From Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles (2018) · cites this paper as Weichert et al., 2016
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Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles
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- Authors
- Weichert, M., Lichius, A., Priegnitz, B.-E., Brandt, U., Gottschalk, J., Nawrath, T., Groenhagen, U., Read, N. D., Schulz, S., & Fleißner, A.
- Affiliations
- Technische Universität Braunschweig (DE)
- Universität Innsbruck (AT)
- University of Manchester (GB)
- Corresponding author
- Fleißner, André
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-10-05
- Volume
- 113
- Issue
- 42
- Pages
- 11877-11882
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5081648
- OpenAlex
- W2529489921
- Cited by
- 35
- References
- 36
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 8 · 2019: 5 · 2018: 6 · 2017: 1
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (FL706-2)
- European Commission (PITN-GA-2013-607963)
- Biotechnology and Biological Sciences Research Council (BB/E010741/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- sterol precursors, ergosterol, sterol biosynthesis, cell fusion, intercellular communication, MAPK signaling, Neurospora crassa, spore germination, conjugated double bonds
- MeSH terms
- Cell Communication, Cell Fusion, Enzyme Activation, Ergosterol, Fungal Proteins, Mutation, Neurospora crassa, Phenotype, Protein Binding, Sterols, Biomarkers, Gene Expression, Gene Deletion, Genes, Reporter, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Hyphae, Protein Kinase Inhibitors, Ether-A-Go-Go Potassium Channels
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