Accumulation of specific sterol precursors targets a MAP kinase cascade mediating cell–cell recognition and fusion

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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Faculty Opinions recommendation of Structural basis of eukaryotic cell-cell fusion.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718348654.793494093 ◽

2014 ◽

Author(s):

David Tareste

Keyword(s):

Cell Fusion ◽

Eukaryotic Cell ◽

Structural Basis ◽

Cell Cell

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Faculty Opinions recommendation of Structural basis of eukaryotic cell-cell fusion.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718348654.793498477 ◽

2014 ◽

Author(s):

Chantal Abergel

Keyword(s):

Cell Fusion ◽

Eukaryotic Cell ◽

Structural Basis ◽

Cell Cell

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A network of MAP-Kinase pathways and transcription factors regulates cell-to-cell communication and cell wall integrity in Neurospora crassa

10.1101/281931 ◽

2018 ◽

Author(s):

Monika S. Fischer ◽

Vincent W. Wu ◽

Ji E. Lee ◽

Ronan C. O’Malley ◽

N. Louise Glass

Keyword(s):

Cell Wall ◽

Transcription Factors ◽

Map Kinase ◽

Neurospora Crassa ◽

Cell Fusion ◽

Regulatory Network ◽

Cell Communication ◽

Cell Wall Integrity ◽

Cell Integrity ◽

Map Kinase Pathways

ABSTRACTMaintenance of cell integrity and cell-to-cell communication are fundamental biological processes. Filamentous fungi, such as Neurospora crassa, depend on communication to locate compatible cells, coordinate cell fusion, and establish a robust hyphal network. Two MAP-Kinase pathways are essential for communication and cell fusion in N. crassa; the Cell Wall Integrity/MAK-1 pathway and the MAK-2 (signal response) pathway. Previous studies have demonstrated several points of cross talk between the MAK-1 and MAK-2 pathways, which is likely necessary for oordinating chemotropic growth toward an extracellular signal, and then mediating cell fusion. Canonical MAP-Kinase pathways begin with signal reception and end with a transcriptional response. Two transcription factors, ADV-1 and PP-1, are essential for communication and cell fusion. PP-1 is the conserved target of MAK-2, while it is unclear what targets ADV-1. We did RNAseq on Δadv-1, Δpp-1, and wild-type cells and found that ADV-1 and PP-1 have a shared regulon including many genes required for communication, cell fusion, growth, development, and stress response. We identified ADV-1 and PP-1 binding sites across the genome by adapting the in vitro method of DNA-Affinity Purification sequencing (DAP-seq) for N. crassa. To elucidate the regulatory network, we misexpressed each transcription factor in each upstream MAPK deletion mutant. Misexpression of adv-1 was sufficient to fully suppress the phenotype of the Δpp-1 mutant and partially suppress the phenotype of the Δmak-1 mutant. Collectively, our data demonstrate that the MAK-1-ADV-1 and MAK-2- PP-1 pathways form a tight regulatory network that maintains cell integrity and mediates communication and cell fusion.

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Eukaryotic Cell–Cell Fusion Families

Current Topics in Membranes ◽

10.1016/b978-0-12-385891-7.00009-x ◽

2011 ◽

pp. 209-234 ◽

Cited By ~ 25

Author(s):

Ori Avinoam ◽

Benjamin Podbilewicz

Keyword(s):

Cell Fusion ◽

Eukaryotic Cell ◽

Cell Cell

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The JIP Group of Mitogen-Activated Protein Kinase Scaffold Proteins

Molecular and Cellular Biology ◽

10.1128/mcb.19.10.7245 ◽

1999 ◽

Vol 19 (10) ◽

pp. 7245-7254 ◽

Cited By ~ 314

Author(s):

Jun Yasuda ◽

Alan J. Whitmarsh ◽

Julie Cavanagh ◽

Manoj Sharma ◽

Roger J. Davis

Keyword(s):

Protein Kinase ◽

Map Kinase ◽

Map Kinases ◽

Scaffold Proteins ◽

Mitogen Activated Protein Kinase ◽

Signaling Mechanism ◽

Jnk Pathway ◽

Mitogen Activated Protein ◽

Kinase Cascade ◽

Protein Kinase Cascade

ABSTRACT Activation of the c-Jun NH2-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases is mediated by a protein kinase cascade. This signaling mechanism may be coordinated by the interaction of components of the protein kinase cascade with scaffold proteins. The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates signaling by the mixed-lineage kinase (MLK)→MAP kinase kinase 7 (MKK7)→JNK pathway. The scaffold proteins JIP1 and JIP2 interact to form oligomeric complexes that accumulate in peripheral cytoplasmic projections extended at the cell surface. The JIP proteins function by aggregating components of a MAP kinase module (including MLK, MKK7, and JNK) and facilitate signal transmission by the protein kinase cascade.

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Yeast homolog of mammalian mitogen-activated protein kinase, FUS3/DAC2 kinase, is required both for cell fusion and for G1 arrest of the cell cycle and morphological changes by the cdc37 mutation

Journal of Cell Science ◽

10.1242/jcs.107.9.2617 ◽

1994 ◽

Vol 107 (9) ◽

pp. 2617-2622 ◽

Cited By ~ 1

Author(s):

H.A. Fujimura

Keyword(s):

Protein Kinase ◽

Map Kinase ◽

Cell Fusion ◽

Morphological Changes ◽

Mitogen Activated Protein Kinase ◽

G1 Arrest ◽

Positive Role ◽

Mitogen Activated Protein ◽

Yeast Homolog

Saccharomyces cerevisiae FUS3/DAC2 protein kinase, a homolog of mammalian mitogen-activated protein (MAP) kinase, inactivates a G1 cyclin encoded by the CLN3 gene to arrest cell division in the G1 phase and activates a transcriptional factor STE12 in response to mating pheromone during sexual conjugation. To elucidate the role of the FUS3/DAC2 gene product in the mating process, I constructed and characterized dac2 cln3 double mutants. Here, I show that FUS3/DAC2 is required for completion of cell fusion even in the dac2 cln3 double mutants in which the pheromone response is restored, suggesting that FUS3/DAC2 plays a positive role in cell fusion during conjugation. In addition, the cdc dac2 and cdc37 ste double mutants were constructed and investigated for their phenotypes to clarify the relationship between FUS3/DAC2, STE7 or STE11 and CDC gene products (CDC28, 36, 37 and 39). The results indicate that FUS3/DAC2 may act upstream of CDC28 and provide evidence that the G1 arrest and morphological changes conferred by the cdc37 mutation may require FUS3/DAC2 (MAP kinase), STE7(MEK) and STE11 (MEK kinase).

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The role of vegetative cell fusions in the lifestyle of the wheat fungal pathogen Zymoseptoria tritici

10.1101/2020.01.26.918797 ◽

2020 ◽

Author(s):

Carolina Sardinha Francisco ◽

Maria Manuela Zwyssig ◽

Javier Palma-Guerrero

Keyword(s):

Map Kinase ◽

Vegetative Cell ◽

Cell Communication ◽

Fungal Growth ◽

Zymoseptoria Tritici ◽

Signaling Mechanism ◽

Functional Conservation ◽

Body Development ◽

Cell Fusions

AbstractThe ability of fungal cells to undergo cell fusion allows them to maximize their overall fitness. In this study, we characterized the role of the so gene orthologous in Zymoseptoria tritici and the biological contribution of vegetative cell fusions in the lifestyle of this latent necrotrophic fungus. Firstly, we show that Z. tritici undergoes self-fusion between distinct cellular structures and its mechanism is dependent on the initial cell density. Next, the deletion of ZtSo resulted in the loss of cell-to-cell communication affecting both hyphal and germlings fusion. We show that Z. tritici mutants for MAP kinase-encoding ZtSlt2 (orthologous MAK-1) and ZtFus3 (orthologous MAK-2) genes also fail to undergo self-stimulation and self-fusion, demonstrating the functional conservation of this signaling mechanism across species. Additionally, the ΔZtSo mutant was severely impaired in melanization, which leads us to identify a trade-off between fungal growth and melanization. Though it has been proposed that So is a scaffold protein for MAP kinase genes from the CWI pathway, its deletion did not affect the cell wall integrity of the fungus. Finally, we demonstrated that anastomose is dispensable for pathogenicity, but essential for the fruiting body development and its absence abolish the asexual reproduction of Z. tritici. Taken together, our data show that ZtSo is required for fungal development, while vegetative cell fusions are essential for fungal fitness.

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Faculty Opinions recommendation of Structural basis of eukaryotic cell-cell fusion.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718348654.793494088 ◽

2014 ◽

Author(s):

Alexander Ploss ◽

Gisa Gerold

Keyword(s):

Cell Fusion ◽

Eukaryotic Cell ◽

Structural Basis ◽

Cell Cell

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Angiotensin II regulation of neuromodulation: downstream signaling mechanism from activation of mitogen-activated protein kinase.

The Journal of Cell Biology ◽

10.1083/jcb.135.6.1609 ◽

1996 ◽

Vol 135 (6) ◽

pp. 1609-1617 ◽

Cited By ~ 41

Author(s):

D Lu ◽

H Yang ◽

M K Raizada

Keyword(s):

Angiotensin Ii ◽

Map Kinase ◽

Signaling Pathway ◽

Mitogen Activated Protein Kinase ◽

Receptor Subtype ◽

Ang Ii ◽

Signaling Mechanism ◽

Downstream Signaling ◽

Neuronal Soma ◽

Mitogen Activated Protein

Angiotensin II (Ang II) stimulates expression of tyrosine hydroxylase and norepinephrine transporter genes in brain neurons; however, the signal-transduction mechanism is not clearly defined. This study was conducted to determine the involvement of the mitogen-activated protein (MAP) kinase signaling pathway in Ang II stimulation of these genes. MAP kinase was localized in the perinuclear region of the neuronal soma. Ang II caused activation of MAP kinase and its subsequent translocation from the cytoplasmic to nuclear compartment, both effects being mediated by AT1 receptor subtype. Ang II also stimulated SRE- and AP1-binding activities and fos gene expression and its translocation in a MAP kinase-dependent process. These observations are the first demonstration of a downstream signaling pathway involving MAP kinase in Ang II-mediated neuromodulation in noradrenergic neurons.

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