Oakley Berl, Peñalva Miguel A
Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, United States.
Department of Molecular and Cellular Biosciences, Centro de Investigaciones Biológicas Margarita Salas, Madrid 28040, Spain.
Fungal Genet Biol. 2025 Jun 20;180:104018. doi: 10.1016/j.fgb.2025.104018.
Hyphal tip growth, the primary growth form in fungi, has not yielded its secrets easily or completely, but decades of research in many labs have greatly clarified this fascinating process. In this review, we will summarize progress that has been made in understanding the multiple roles microtubule and microfilament cytoskeletal networks play in tip growth. We will give particular attention to work in Aspergillus nidulans in which these subjects have been studied most intensely, but we will include findings obtained with other organisms where appropriate. Microtubules play a critical role in long range vesicular transport which is powered by the plus end-directed kinesin motor molecules KinA (a type 1 kinesin) and UncA (a type 3 kinesin). The minus end directed motor, dynein, plays an important role in moving kinesins and other cargos away from the hyphal apex so that they can be reused. Actin microfilaments and the motor molecule myosin V play an equally important role, and we will discuss the mechanisms by which microtubule- and actin-dependent transport cooperate to sustain rapid tip growth. With several motors operating in the same cytoplasm, adapter molecules are required to provide the mechanisms by which motors discriminate among cargos. These adapters are being identified and the critical roles of small GTPases are becoming increasingly clear. Endocytosis and exocytosis at the hyphal apex are absolutely required for tip growth and many of the key molecules in these processes have now been identified and their roles clarified. Myosin V is critical for concentrating vesicles carrying vesicular SNAREs at the Spitzenkörper. They then fuse with the apical membrane driven by interaction of vesicular (R-)SNAREs with target (Q-)SNAREs. Localization of the small GTPase RAB11 to the apex is likely a critical marker for the site of exocytosis. Actin patches are the major site of endocytosis, forming a collar near the apex in rapidly growing tip cells, and important progress has been made in understanding the roles of components of actin patches. In total, the machinery for delivering vesicles to the cell apex, the exocytosis machinery and the endocytosis machinery collectively interact to form a tip growth apparatus. Although we celebrate the progress that has been made, we will also point out some of the important remaining questions in this field.
菌丝顶端生长是真菌的主要生长形式，其奥秘难以轻易或完全揭开，但许多实验室数十年的研究已极大地阐明了这一迷人的过程。在本综述中，我们将总结在理解微管和微丝细胞骨架网络在顶端生长中所起的多种作用方面取得的进展。我们将特别关注构巢曲霉中的研究工作，在该真菌中这些主题已得到最深入的研究，但我们也将酌情纳入其他生物体的研究发现。微管在由正端定向的驱动蛋白分子KinA（一种1型驱动蛋白）和UncA（一种3型驱动蛋白）驱动的长距离囊泡运输中起关键作用。负端定向的动力蛋白——动力蛋白，在将驱动蛋白和其他货物从菌丝顶端移开以便它们能够被重新利用方面发挥着重要作用。肌动蛋白微丝和驱动蛋白分子肌球蛋白V发挥着同样重要的作用，我们将讨论微管依赖性运输和肌动蛋白依赖性运输协同维持快速顶端生长的机制。由于几种驱动蛋白在同一细胞质中起作用，因此需要衔接分子来提供驱动蛋白区分货物的机制。这些衔接分子正在被识别，小GTP酶的关键作用也越来越清晰。菌丝顶端的内吞作用和外排作用对于顶端生长绝对必要，并且这些过程中的许多关键分子现已被识别，其作用也已阐明。肌球蛋白V对于将携带囊泡SNARE的囊泡聚集在Spitzenkörper至关重要。然后，它们在囊泡（R-）SNARE与靶标（Q-）SNARE相互作用的驱动下与顶端膜融合。小GTP酶RAB11定位于顶端可能是胞吐作用位点的关键标志物。肌动蛋白斑是内吞作用的主要位点，在快速生长的顶端细胞中在顶端附近形成一个环，并且在理解肌动蛋白斑成分的作用方面已取得重要进展。总的来说，将囊泡递送至细胞顶端的机制、胞吐作用机制和内吞作用机制共同相互作用形成一个顶端生长装置。尽管我们对已取得的进展表示赞赏，但我们也将指出该领域一些重要的遗留问题。
