Földi István, Tóth Krisztina, Gombos Rita, Gaszler Péter, Görög Péter, Zygouras Ioannis, Bugyi Beáta, Mihály József
Biological Research Centre, Institute of Genetics, Eötvös Loránd Research Network, Temesvári krt. 62, H-6726 Szeged, Hungary.
Doctoral School of Multidisciplinary Medical Science, Faculty of Medicine, University of Szeged, H-6725 Szeged, Hungary.
Cells. 2022 Apr 28;11(9):1487. doi: 10.3390/cells11091487.
Axonal growth is mediated by coordinated changes of the actin and microtubule (MT) cytoskeleton. Ample evidence suggests that members of the formin protein family are involved in the coordination of these cytoskeletal rearrangements, but the molecular mechanisms of the formin-dependent actin-microtubule crosstalk remains largely elusive. Of the six formins, DAAM was shown to play a pivotal role during axonal growth in all stages of nervous system development, while FRL was implicated in axonal development in the adult brain. Here, we aimed to investigate the potentially redundant function of these two formins, and we attempted to clarify which molecular activities are important for axonal growth. We used a combination of genetic analyses, cellular assays and biochemical approaches to demonstrate that the actin-processing activity of DAAM is indispensable for axonal growth in every developmental condition. In addition, we identified a novel MT-binding motif within the FH2 domain of DAAM, which is required for proper growth and guidance of the mushroom body axons, while being dispensable during embryonic axon development. Together, these data suggest that DAAM is the predominant formin during axonal growth in , and highlight the contribution of multiple formin-mediated mechanisms in cytoskeleton coordination during axonal growth.
轴突生长由肌动蛋白和微管（MT）细胞骨架的协同变化介导。大量证据表明，formin蛋白家族成员参与了这些细胞骨架重排的协调，但formin依赖的肌动蛋白-微管串扰的分子机制仍 largely难以捉摸。在六种formin中，DAAM在神经系统发育的所有阶段的轴突生长过程中都起着关键作用，而FRL与成年大脑中的轴突发育有关。在这里，我们旨在研究这两种formin的潜在冗余功能，并试图阐明哪些分子活性对轴突生长很重要。我们结合了遗传分析、细胞试验和生化方法，以证明DAAM的肌动蛋白加工活性在每种发育条件下对轴突生长都是不可或缺的。此外，我们在DAAM的FH2结构域内鉴定了一个新的MT结合基序，这是蘑菇体轴突正常生长和导向所必需的，而在胚胎轴突发育过程中是可有可无的。总之，这些数据表明DAAM是轴突生长过程中的主要formin，并突出了多种formin介导的机制在轴突生长过程中细胞骨架协调中的作用。
