对LATS1和LATS2的紧张依赖定位的调节
bioRxiv : the preprint server for biology
|September 5, 2025
概括
LIMD1将LATS1/ 2激酶引入细胞结点,调节Hippo通路. 这种结合依赖于LIMD1
科学领域:
- 细胞生物学
- 分子机制
- 信号传输
背景情况:
- 河马的信号通路对于器官大小的控制至关重要,
- 已知LIM域蛋白1 (LIMD1) 与Hippo路径激酶LATS1/ 2相互作用.
- LIMD1在机械应力下将LATS1/ 2隔离到粘附结 (AJs) 的作用已确定,但其分子基础尚不清楚.
研究的目的:
- 阐明LIMD1对LATS1/2的结合和招募的分子机制.
- 确定LIMD1内负责LATS1/2相互作用和定位的特定域和动机.
- 了解机械应变如何影响Hippo通路内的LIMD1-LATS1/2相互作用.
主要方法:
- 使用AlphaFold建模来预测蛋白质相互作用并识别保存的图案.
- 进行生物化学测试以确认蛋白质结合相互作用.
- 采用基于细胞的局部化试验来可视化蛋白质对粘附结的招募.
- 在LIMD1和LATS1/2中引入点突变以评估功能要求.
主要成果:
- LIMD1的LIM域足以进行AJ定位和LATS1/2结合,但需要N端IDR和LIM域进行招募.
- LIMD1的LIM1和LIM2域对LATS1 AJ局部化至关重要;破坏菌株敏感性的突变取消了结合和招募.
- 在LIMD1中鉴定出一种保存的LATS-LATCH基因,这种基因对于依赖于菌株的LATS1/2征集至关重要且足够;突变会破坏结合和局部化.
结论:
- 一个涉及LIM域-LATCH相互作用和N端IDR函数的双重机制调解了LIMD1 / 2依赖的LATS1 / 2招募.
- 这种机制可以了解机械信号是如何通过Hippo路径转换的.
- 这种LATS-LATCH基因是LIMD1对应变敏感性Hippo通路调节的关键媒介.
相关概念视频
Tension Response at Adherens Junctions
2.8K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.8K
Intracellular Signaling Affects Focal Adhesions
2.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.8K
Adherens Junctions
5.0K
Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types – adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
Adherens Junctions are Dynamic
5.0K
Anchoring Junctions
3.9K
Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
3.9K
Cytoskeletal Coordination in Cell Migration
4.9K
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
4.9K
Catenins
2.4K
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.4K


