Cytoskeletal adaptation following long-term dysregulation of actomyosin in neuronal processes.
Cytoskeletal adaptation following long-term dysregulation of actomyosin in neuronal processes.
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神经元过程中肌动球蛋白长期失调后的细胞骨架适应。
DOI：
10.1101/2023.08.25.554891
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Vitriol,EricA
中科院分区：
文献类型：
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作者：
Cisterna,BrunoA;Skruber,Kristen;Jane,MakenzieL;Camesi,CalebI;Nguyen,IvanD;Warp,PeytonV;Black,JosephB;Butler,MitchellT;Bear,JamesE;Tracy-Ann,Read;Vitriol,EricA
除了其在肌动蛋白组装中的公认作用外，已显示Profilin 1（PFN1）与微管蛋白结合并改变微管的聚合。然而，PFN1对细胞中微管的主要控制是通过微管蛋白的直接调节还是通过肌动蛋白的聚合间接发生的还有待确定。在这里，我们操纵PFN1的表达，肌动蛋白丝组装和肌动球蛋白收缩性，并表明，减少任何这些增加微管的数量和乙酰化，与效果显着更显着的神经过程。如果肌动球蛋白收缩性恢复，微管的变化是可逆的，认为PFN1对微管的调节主要通过肌动蛋白发生。此外，PFN1耗竭导致的神经元过程中微管的改变导致基于微管的转运发生显著变化，模拟与神经退行性疾病相关的表型。因此，肌动蛋白动力学的缺陷会引起其他细胞骨架成分的代偿反应，深刻影响细胞功能。
In addition to its well-established role in actin assembly, Profilin 1 (PFN1) has been shown to bind to tubulin and alter the polymerization of microtubules. However, whether PFN1’s predominant control over microtubules in cells occurs through direct regulation of tubulin or indirectly through the polymerization of actin has yet to be determined. Here we manipulated PFN1 expression, actin filament assembly, and actomyosin contractility and showed that reducing any of these increases the number and acetylation of microtubules, with the effect being significantly more pronounced in neuronal processes. Changes to microtubules are reversible if actomyosin contractility is restored, arguing that PFN1’s regulation of microtubules occurs principally through actin. Moreover, the altered microtubules in neuronal processes resulting from PFN1 depletion cause significant changes to microtubule-based transport, mimicking phenotypes that are linked to neurodegenerative disease. Thus, defects in actin dynamics cause a compensatory response in other cytoskeleton components, profoundly effecting cellular function.