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UNIGE study reveals how enzymes locally block cell wall repair, allowing cells to fuse in an irreversible manner.
The fusion of two cells is a decisive event in the sexual reproduction of many organisms. In fungi, cells must not only bring their membranes together and merge them, but also locally open their protective cell wall. A study conducted at the University of Geneva (UNIGE) shows how a mechanism that prevents cells from repairing their wall at the fusion site makes this process irreversible. Published in the journal Current Biology, these findings provide new insights into how cells coordinate fusion and repair mechanisms and could ultimately open new avenues for targeting the cell wall of pathogenic fungi.
Unlike animal cells, fungal cells are surrounded by a rigid cell wall. This structure protects them and allows them to withstand the internal pressure exerted by their cellular contents. When two cells fuse, notably during sexual reproduction, this wall must be locally degraded to allow the membranes of the two cells to merge. Once this step has been completed, fusion normally proceeds until a single cell is formed.
An irreversible fusion
However, because the integrity of the cell wall is essential for cell survival, it is constantly monitored to trigger repair mechanisms in response to damage. The existence of these two apparently opposing processes led the team of Sophie Martin, professor in the Section of Biology of the Faculty of Science at UNIGE, to investigate how cells prevent their repair system from rebuilding the wall during cell fusion.
The team studied Schizosaccharomyces pombe, a single-celled yeast widely used as a model organism to understand fundamental cellular mechanisms. The researchers had previously identified mutant yeasts lacking the enzyme Pak2, which display transient fusion: the cells briefly fuse and begin exchanging cellular contents before separating again, with catastrophic consequences for the cells.
The cell wall is a major target of many treatments against pathogenic fungi.
The biologists observed that, in normal cells, the enzyme Pak2 accumulates precisely at the site where the two cells fuse. Its activity promotes the opening and subsequent expansion of the "fusion pore", the opening that allows cellular contents to pass from one cell to the other.
"However, when Pak2 is absent, the process can sometimes become reversible: the cells begin to fuse, exchange their contents, and then close the opening that connected them. In these cells, we observe that the mechanisms normally responsible for monitoring and repairing the cell wall become particularly active at the fusion site," explains Julia Coronas-Serna, former postdoctoral researcher in Sophie Martin's group and first author of the study.
A rebuilt wall after a failed fusion
Using advanced imaging techniques, the scientists observed the internal organization of cells lacking the Pak2 enzyme, particularly at the site where the two cells are in contact. "After the fusion pore closes in these mutant cells, we observe the formation of a new cell wall at the interface between the two cells. In other words, when the mechanisms that prevent repair are absent, the cell can literally rebuild the separation it had begun to dismantle," explains Sophie Martin.
By identifying the mechanisms that control the balance between cell wall repair and its localized degradation during fusion, these results open new avenues for the search for antifungal strategies. The cell wall is a major target of many treatments against pathogenic fungi such as Candida and Aspergillus, which are responsible for infections in humans. A better understanding of the mechanisms regulating its formation and repair could ultimately help identify new molecules capable of disrupting these processes.
