在LMNA心肌病中,微管体力驱动核损伤
Daria Amiad Pavlov1, Julie Heffler2, Carmen Suay-Corredera1
1Department of Physiology, Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania.
bioRxiv : the preprint server for biology
|July 1, 2024
概括
破坏微管,而不是LINC复合体,可以防止层层A/C缺陷心脏的核损伤. 这一发现为LMNA相关心肌病症提供了一个新的治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 心血管研究研究心血管研究
背景情况:
- 核平衡依赖于细胞骨和核力平衡.
- 在LMNA中发生的突变会削弱核膜,导致核损伤和肌肉疾病.
- 林克复合干扰是LMNA相关心肌病的潜在治疗方法,但其机制尚不清楚.
研究的目的:
- 为了研究LINC复杂干扰如何保护心肌细胞核.
- 量化心肌细胞收缩和核变形之间的关系.
- 确定核膜和LINC复合体在这个过程中的作用.
主要方法:
- 开发了一种测试方法来测量心肌细胞收缩-核变形合.
- 研究了LINC复合体中断对层层A/C缺陷细胞中核菌株的影响.
- 利用计算模拟来建模核应力场.
主要成果:
- 这种LINC复合体在很大程度上是不可或缺的,可以将收缩性应变传递到核中.
- 在LINC复合体中断并没有挽救层层A/C缺陷细胞中增加的核应变.
- 破坏围绕核的微管,可以防止核损伤,改善心脏功能.
结论:
- 局部化,微管体依赖的力传递是LMNA心肌病的关键因素.
- 微管破坏是LMNA相关心肌病的有前途的治疗策略.
- 准微管核相互作用可能为治疗由LMNA突变引起的肌肉疾病提供新的途径.
更多相关视频
06:23Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence
Published on: January 17, 2025
692
16:27Biophysical Assays to Probe the Mechanical Properties of the Interphase Cell Nucleus: Substrate Strain Application and Microneedle Manipulation
Published on: September 14, 2011
12.4K
相关概念视频
Destabilization of Microtubules
2.7K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.7K
Microtubule Instability
5.1K
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
5.1K
Drugs that Stabilize Microtubules
2.0K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.0K
Drugs that Destabilize Microtubules
2.0K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
Anaphase A and B
4.0K
Microtubules form through the end-to-end polymerization of tubulin heterodimers. Kinetochore microtubules originate from the spindle poles, and their plus-ends connect with the kinetochores on sister-chromatids. Ndc80 protein complexes, present on the kinetochore, form low-affinity links with the plus end of these kinetochore microtubules.
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
4.0K
Disassembly of Intermediate Filaments
2.1K
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
2.1K
