新的神经元细胞骨架调节蛋白被发现-动脉网

New regulatory protein of the neuronal cytoskeleton identified

D-Pharm 等信源发布 2025-04-28 11:38

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The growth and function of

生长和功能

nerve cells

神经细胞

is based on a lattice-like structure called membrane-associated periodic skeleton (MPS). However, how the organization of the MPS is controlled has not been elucidated until now. A team from the Max Planck Institutes for Medical Research and for Multidisciplinary Sciences has now discovered that it is regulated by the concentration of the protein paralemmin-1..

基于一种称为膜相关周期性骨架（MPS）的类晶格结构。然而，直到现在，MPS的组织是如何被控制的仍未得到阐明。来自马克斯·普朗克医学研究所和多学科科学研究所的一个团队现已发现，它受到蛋白质paralemmin-1浓度的调控。

Key role of paralemmin-1 identified

已确定Paralemmin-1的关键作用

Nature has developed a unique structure as a scaffold for almost all nerve cells: the membrane-associated periodic skeleton, MPS. This specialized cytoskeletal structure is located below the cell membrane and consists of numerous proteins in a periodic arrangement. The MPS is involved in various cellular processes, such as inter- and intracellular signaling.

自然界已发展出一种独特的结构，作为几乎所有神经细胞的支架：膜相关周期性骨架（MPS）。这种特殊的细胞骨架结构位于细胞膜下方，由大量以周期性排列的蛋白质组成。MPS 参与了多种细胞过程，例如细胞间和细胞内的信号传导。

To date, many proteins have been identified that interact with the MPS, but the mechanisms underlying its organization are not yet fully understood. .

到目前为止，已经鉴定出许多与 MPS 相互作用的蛋白质，但其组织背后的机制尚未完全了解。

“Our work started with the question of whether paralemmin-1 is associated with the MPS in neurons,” explains Victor Macarrón-Palacios of the Max Planck Institute (MPI) for Medical Research in Heidelberg. “Ultimately, we were able to show that paralemmin-1 is indeed associated and that it also plays a key role: It regulates the organization of the MPS.”.

“我们的工作始于一个疑问，即paralemmin-1是否与神经元中的MPS相关，”海德堡马克斯·普朗克医学研究所（MPI）的维克多·马卡龙-帕拉西奥斯解释道。“最终，我们能够证明paralemmin-1确实与之相关，并且它还起到了关键作用：它调节了MPS的组织结构。”

Nanoscopy provide crucial insights

纳米显微技术提供了关键的见解

Visualizing the MPS is not possible with conventional microscopy techniques, only with nanoscopy. For their study, the scientists at the MPI for Medical Research used state-of-the-art fluorescence nanoscopy: the STED- and MINFLUX microscopy for which Max Planck director Stefan Hell was awarded the Nobel Prize in Chemistry in 2014..

使用常规显微技术无法观察到MPS，只能通过纳米显微技术实现。在他们的研究中，马克斯·普朗克医学研究所的科学家使用了最先进的荧光纳米显微技术：STED和MINFLUX显微镜，马克斯·普朗克主任斯特凡·赫尔因该技术于2014年获得了诺贝尔化学奖。

A collaboration between the MPI for Medical Research and the MPI for Multidisciplinary Sciences in Göttingen led to this successful project. Manfred W. Kilimann, retired university professor and guest researcher at the MPI for Multidisciplinary Sciences, initiated the study and provided the team in Heidelberg led by Elisa D’Este with the results and materials compiled in his laboratory.

马克斯·普朗克医学研究所与哥廷根的马克斯·普朗克多学科科学研究所之间的合作促成了这一成功的项目。退休大学教授、马克斯·普朗克多学科科学研究所的客座研究员曼弗雷德·W·基利曼发起了这项研究，并将他在实验室中编译的结果和材料提供给了由埃尔莎·德斯特领导的海德堡团队。

This enabled Victor Macarrón-Palacios to investigate the neural cytoskeleton in his doctoral thesis. These discoveries were further complemented by biochemical techniques and the expertise and support of the entire scientific team: a perfect example of interdisciplinary collaboration and synergy between the two institutes.

这使得维克多·马卡龙-帕拉西奥斯在他的博士论文中研究神经细胞骨架。这些发现还通过生物化学技术以及整个科学团队的专业知识和支持得到了进一步的补充：这是两个研究所之间跨学科合作和协同作用的完美例子。

Further contributions to this research work came from scientists at the universities of Heidelberg and Uppsala (Sweden)..

这项研究工作的进一步贡献来自海德堡大学和乌普萨拉大学（瑞典）的科学家。

The researchers were able to show that the concentration of paralemmin-1 is of fundamental importance for controlling the nanoscale organization of the periodic scaffold of the cytoskeleton: “High levels of paralemmin-1 result in an extremely tight periodic arrangement, while lower levels lead to a poorly organized MPS,” reports Manfred W.

研究人员能够证明，paralemmin-1 的浓度对于控制细胞骨架周期性支架的纳米级组织至关重要：“高水平的 paralemmin-1 会导致极其紧密的周期性排列，而较低水平则会导致组织不良的 MPS，”Manfred W. 报道。

Kilimann. Moreover, the absence of paralemmin-1 affects the electrophysiological properties of the neurons, specifically the electrical signal transmission between them. The team was also able to show that paralemmin-1's ability to fulfill its function depends on a single tryptophan amino acid, W54..

基里曼。此外，缺少类膜蛋白-1会影响神经元的电生理特性，特别是它们之间的电信号传递。团队还能够证明，类膜蛋白-1履行其功能的能力取决于单一的色氨酸氨基酸W54。

A deeper understanding of the paralemmin protein family and MPS

对paralemmin蛋白家族和MPS的更深入理解

“By studying paralemmin-1, we have identified a mechanism that regulates the fine structure of the MPS in neurons,” explains Victor Macarrón-Palacios. In this process, paralemmin-1 binds the protein ßII-spectrin, a major component of the neuronal cytoskeleton, in a domain that is prone to mutations.

“通过研究类突触蛋白-1，我们已经确定了调节神经元中MPS精细结构的机制，”维克多·马卡龙-帕拉西奥斯解释道。在此过程中，类突触蛋白-1会与神经元细胞骨架的主要组成部分ßII-血影蛋白在一个容易发生突变的区域结合。

These mutations are responsible for neurological developmental disorders in humans. There is great potential for further research here – the function and regulation of the MPS are only just beginning to emerge..

这些突变是导致人类神经发育障碍的原因。这里还有很大的研究潜力——MPS的功能和调控机制才刚刚开始被揭示。

Original publication

最初出版

Victor Macarrón-Palacios, Jasmine Hubrich, Maria Augusta do Rego Barros Fernandes Lima, Nicole G. Metzendorf, Simon Kneilmann, Marleen Trapp, Claudio Acuna, Annarita Patrizi, Elisa D’Este, Manfred W. Kilimann; 'Paralemmin-1 controls the nanoarchitecture of the neuronal submembrane cytoskeleton'; Science Advances, Volume 11.

维克多·马卡龙-帕拉西奥斯，贾斯敏·胡布里希，玛丽亚·奥古斯塔·雷戈·巴罗斯·费尔南德斯·利马，妮可·G·梅岑多夫，西蒙·克内尔曼，马琳·特拉普，克劳迪奥·阿库纳，安娜丽塔·帕特里齐，伊丽莎·D’埃斯特，曼弗雷德·W·基利曼；《Paralemmin-1控制神经元亚膜细胞骨架的纳米结构》；《科学进展》，第11卷。

https://www.bionity.com/en/news/1186115/new-regulatory-protein-of-the-neuronal-cytoskeleton-identified.html

https://www.bionity.com/zh/news/1186115/新发现的神经元细胞骨架调控蛋白.html

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