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细胞外黏附信号物理性地定义了核仁的结构和功能。

Extracellular Adhesive Cues Physically Define Nucleolar Structure and Function.

机构信息

Centre for Cell Biology and Cutaneous Research, 4 Newark Street, London, E1 2AT, UK.

出版信息

Adv Sci (Weinh). 2022 Apr;9(10):e2105545. doi: 10.1002/advs.202105545. Epub 2022 Feb 5.

DOI:10.1002/advs.202105545
PMID:35122409
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8981897/
Abstract

Adhesive cues from the extracellular matrix (ECM) specify the size and shape of the nucleus via mechanical forces transmitted through the cytoskeleton. However, the effects of these biophysical stimuli on internal nuclear architecture and cellular responses remain poorly understood. This study investigates the direct impact of ECM adhesion on nucleolar remodeling in human keratinocytes using micropatterned substrates. Limited adhesion on small micropatterns promotes fusion of nucleoli, alongside a reduction in nuclear volume and condensation of heterochromatin. These changes in nucleolar architecture are mediated by altered chromatin biomechanics and depend on integration of the nucleus with the actin cytoskeleton. Functionally, nucleolar remodeling regulates ribogenesis and protein synthesis in keratinocytes and is associated with specific transcriptional changes in ribogenesis genes. Together, these findings demonstrate that cell shape and nuclear morphology control nucleolar structure and function and implicate the nucleolus as a key mechano-sensing element within the cell.

摘要

细胞外基质（ECM）中的黏附信号通过细胞骨架传递的机械力来指定核的大小和形状。然而，这些生物物理刺激对内核结构和细胞反应的影响仍知之甚少。本研究使用微图案化基底研究 ECM 黏附对人角质形成细胞核仁重塑的直接影响。在小的微图案上的有限黏附促进核仁融合，同时核体积减小和异染色质凝聚。核仁结构的这些变化是由染色质生物力学的改变介导的，并依赖于细胞核与肌动蛋白细胞骨架的整合。功能上，核仁重塑调节角质形成细胞中的核糖体生成和蛋白质合成，并与核糖体生成基因的特定转录变化相关。总之，这些发现表明细胞形状和核形态控制核仁的结构和功能，并暗示核仁是细胞内的一个关键机械感应元件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/1f3ea670c2b4/ADVS-9-2105545-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/0138750d81a2/ADVS-9-2105545-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/d357b716fb31/ADVS-9-2105545-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/85604b80f3f0/ADVS-9-2105545-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/e8cf6f875dd3/ADVS-9-2105545-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/b2f2b8d904e7/ADVS-9-2105545-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/a8d262697ba7/ADVS-9-2105545-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/1f3ea670c2b4/ADVS-9-2105545-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/0138750d81a2/ADVS-9-2105545-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/d357b716fb31/ADVS-9-2105545-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/85604b80f3f0/ADVS-9-2105545-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/e8cf6f875dd3/ADVS-9-2105545-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/b2f2b8d904e7/ADVS-9-2105545-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/a8d262697ba7/ADVS-9-2105545-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0d/8981897/1f3ea670c2b4/ADVS-9-2105545-g007.jpg

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