Remodeling of the Actin/Spectrin Membrane-associated Periodic Skeleton, Growth Cone Collapse and F-Actin Decrease during Axonal Degeneration.
Remodeling of the Actin/Spectrin Membrane-associated Periodic Skeleton, Growth Cone Collapse and F-Actin Decrease during Axonal Degeneration.
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DOI：
10.1038/s41598-018-21232-0
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发表时间：
2018-02-14
影响因子：
4.6
通讯作者：
Cáceres AO
中科院分区：
文献类型：
--
作者：
Unsain N;Bordenave MD;Martinez GF;Jalil S;von Bilderling C;Barabas FM;Masullo LA;Johnstone AD;Barker PA;Bisbal M;Stefani FD;Cáceres AO
轴突变性发生在发育中的神经系统中，用于适当地建立成熟回路，并且也是多种神经变性疾病的标志。尽管最近在该领域的兴趣，鲜为人知的是轴突变性过程中的细胞骨架的变化（和可能的作用）。我们研究了肌动蛋白细胞骨架在体外模型的发育修剪诱导的营养因子撤退（TFW）。我们发现，F-肌动蛋白减少和生长锥塌陷（GCC）发生后TFW的早期，然而，治疗，防止轴突断裂未能防止GCC，这表明独立的途径。使用超分辨率（STED）显微镜，我们发现，轴突肌动蛋白/血影蛋白膜相关的周期性骨架（MPS）的丰度和组织下降后不久剥夺，保持低，直到碎片。断裂的轴突缺乏MPS（同时维持微管），稳定肌动蛋白丝的急性药物治疗可防止MPS丢失并保护轴突断裂，这表明轴突断裂需要MPS破坏才能进行。
Axonal degeneration occurs in the developing nervous system for the appropriate establishment of mature circuits, and is also a hallmark of diverse neurodegenerative diseases. Despite recent interest in the field, little is known about the changes (and possible role) of the cytoskeleton during axonal degeneration. We studied the actin cytoskeleton in an in vitro model of developmental pruning induced by trophic factor withdrawal (TFW). We found that F-actin decrease and growth cone collapse (GCC) occur early after TFW; however, treatments that prevent axonal fragmentation failed to prevent GCC, suggesting independent pathways. Using super-resolution (STED) microscopy we found that the axonal actin/spectrin membrane-associated periodic skeleton (MPS) abundance and organization drop shortly after deprivation, remaining low until fragmentation. Fragmented axons lack MPS (while maintaining microtubules) and acute pharmacological treatments that stabilize actin filaments prevent MPS loss and protect from axonal fragmentation, suggesting that MPS destruction is required for axon fragmentation to proceed.
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影响因子：
4.6
作者：
D'Este E;Kamin D;Velte C;Göttfert F;Simons M;Hell SW
通讯作者：
Hell SW
影响因子：
3
作者：
Sainath, Rajiv;Gallo, Gianluca
通讯作者：
Gallo, Gianluca
影响因子：
4
作者：
Soerensen, Pia M.;Iacob, Roxana E.;Fritzsche, Marco;Engen, John R.;Brieher, William M.;Charras, Guillaume;Eggert, Ulrike S.
通讯作者：
Eggert, Ulrike S.
DOI：
10.1073/pnas.1605707113
发表时间：
2016-05-24
影响因子：
11.1
作者：
He, Jiang;Zhou, Ruobo;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
4.6
作者：
Barabas, Federico M.;Masullo, Luciano A.;Stefani, Fernando D.
通讯作者：
Stefani, Fernando D.