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着丝粒蛋白对于核周运动(INM)和细胞周期进程是必需的。

Vinculin is required for interkinetic nuclear migration (INM) and cell cycle progression.

机构信息

Instituto de Biología Molecular de Barcelona (CSIC) , Barcelona, Spain.

出版信息

J Cell Biol. 2024 Jan 1;223(1). doi: 10.1083/jcb.202106169. Epub 2023 Oct 27.

Abstract

Vinculin is an actin-binding protein (ABP) that strengthens the connection between the actin cytoskeleton and adhesion complexes. It binds to β-catenin/N-cadherin complexes in apical adherens junctions (AJs), which maintain cell-to-cell adhesions, and to talin/integrins in the focal adhesions (FAs) that attach cells to the basal membrane. Here, we demonstrate that β-catenin targets vinculin to the apical AJs and the centrosome in the embryonic neural tube (NT). Suppression of vinculin slows down the basal-to-apical part of interkinetic nuclear migration (BAINM), arrests neural stem cells (NSCs) in the G2 phase of the cell cycle, and ultimately dismantles the apical actin cytoskeleton. In the NSCs, mitosis initiates when an internalized centrosome gathers with the nucleus during BAINM. Notably, our results show that the first centrosome to be internalized is the daughter centrosome, where β-catenin and vinculin accumulate, and that vinculin suppression prevents centrosome internalization. Thus, we propose that vinculin links AJs, the centrosome, and the actin cytoskeleton where actomyosin contraction forces are required.

摘要

粘着斑蛋白(Vinculin)是一种肌动蛋白结合蛋白(ABP),能够增强细胞骨架肌动蛋白和黏附复合物之间的连接。它与顶端黏着连接(AJ)中的β-连环蛋白/N-钙黏蛋白复合物结合,维持细胞间的黏附,与黏着斑中的桩蛋白/整合素结合,将细胞附着在基底膜上。在这里,我们证明β-连环蛋白将粘着斑蛋白靶向到胚胎神经管(NT)中的顶端 AJ 和中心体。粘着斑蛋白的抑制会减缓核往返迁移(BAINM)的基底到顶端部分,使神经干细胞(NSC)在细胞周期的 G2 期停滞,并最终破坏顶端肌动蛋白细胞骨架。在 NSC 中,有丝分裂在核通过 BAIM 内移期间与内化的中心体聚集时开始。值得注意的是,我们的结果表明,第一个被内化的中心体是子中心体,β-连环蛋白和粘着斑蛋白在那里积累,并且粘着斑蛋白的抑制阻止了中心体的内化。因此,我们提出粘着斑蛋白将 AJ、中心体和肌动球蛋白收缩力所需的细胞骨架连接起来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/867a/10609122/cb4a03071be8/JCB_202106169_GA.jpg

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