Dr. Alexander Lichius from the Institute of Microbiology, University of Innsbruck recently co-authored a paper on the influence of sterole precursors on cell-cell recognition and fusion in Neurospora crassa.

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

Weichert et al., 2016. PNAS 113(42): 11877-11882.


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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The movie shows recruitment of the GFP-labelled MAPK MAK-1 to the cell fusion site between conidial germlings of N. crassa. MAK-1 also resides inside nuclei, but excluded from the nucleolus, and as discrete but highly dynamic cortical clusters along the plasma membrane. Scale bar, 5µm.