Cell-cell fusion is crucial for the development and propagation of most eukaryotic organisms. Despite this importance, the molecular mechanisms mediating this process are only poorly understood in any biological system. In particular, the step of plasma membrane merger and the contributing proteins and physicochemical factors remain mostly unknown. Earlier studies provided first evidence of a role of membrane sterols in cell-cell fusion. By characterizing different ergosterol biosynthesis mutants of the fungus Neurospora crassa, which accumulate different ergosterol precursors, we show that the structure of the sterol ring system specifically affects plasma membrane merger during the fusion of vegetative spore germlings. Genetic analyses pinpoint this defect to an event prior to engagement of the fusion machinery. Strikingly, this effect is not observed during sexual fusion, suggesting that the specific sterol precursors do not generally block membrane merger, but rather impair subcellular processes exclusively mediating fusion of vegetative cells. On a colony-wide level, the altered structure of the sterol ring system affects a subset of differentiation processes, including vegetative sporulation and steps before and after fertilization during sexual propagation. Together these observations corroborate the notion that the accumulation of particular sterol precursors has very specific effects on defined cellular processes rather than non-specifically disturbing membrane functioning. Given the phenotypic similarities of the ergosterol biosynthesis mutants of N. crassa during vegetative fusion and of Saccharomyces cerevisiae cells undergoing mating, our data support the idea that yeast mating is evolutionary and mechanistically more closely related to vegetative than sexual fusion of filamentous fungi.

中文翻译：

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在粗糙脉孢菌的营养发育过程中，质膜融合特别受到膜甾醇分子结构的影响。


细胞与细胞的融合对于大多数真核生物的发育和繁殖至关重要。尽管如此重要，但在任何生物系统中介导这一过程的分子机制却知之甚少。特别是，质膜合并的步骤以及起作用的蛋白质和理化因素仍然大多未知。早期的研究提供了膜甾醇在细胞-细胞融合中的作用的第一个证据。通过表征真菌粗糙脉孢菌的不同麦角甾醇生物合成突变体（其积累不同的麦角甾醇前体），我们表明甾醇环系统的结构在营养孢子幼体融合过程中特异性地影响质膜合并。遗传分析将这一缺陷确定为融合机器参与之前的事件。引人注目的是，在有性融合过程中没有观察到这种效应，这表明特定的甾醇前体通常不会阻止膜合并，而是损害专门介导营养细胞融合的亚细胞过程。在群体范围内，甾醇环系统结构的改变影响分化过程的子集，包括营养孢子形成以及有性繁殖过程中受精前后的步骤。这些观察结果共同证实了这样的观点，即特定甾醇前体的积累对特定的细胞过程具有非常特定的影响，而不是非特定地干扰膜功能。鉴于N.麦角甾醇生物合成突变体的表型相似性。 我们的数据支持这样的观点，即酵母交配在进化和机制上与丝状真菌的营养融合比有性融合更密切相关。