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α-微管蛋白乙酰转移酶 1 的表达和微管蛋白乙酰化作为细胞竞争中的选择力。

Expression of α-Tubulin Acetyltransferase 1 and Tubulin Acetylation as Selective Forces in Cell Competition.

机构信息

GZMB, Johann-Friedrich-Blumenbach-Institute of Zoology and Anthropology-Developmental Biology, Biological Faculty, Georg-August-Universität Göttingen, Ernst-Caspari-Haus, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.

Department of Biology, School of Mathematics, Physics and Natural Sciences, University of Rome Tor Vergata, Via della Ricerca Scientifica, 1-00133 Rome, Italy.

出版信息

Cells. 2021 Feb 14;10(2):390. doi: 10.3390/cells10020390.

Abstract

The wound healing response of fibroblasts critically depends on the primary cilium, a sensory organelle protruding into the environment and comprising a stable axonemal structure. A characteristic marker for primary cilia is acetylation of axonemal tubulin. Although formation of primary cilia is under cell cycle control, the environmental cues affecting ciliation are not fully understood. Our purpose was, therefore, to study the impact of culture conditions on cilia formation in NIH3T3 fibroblasts. We quantified ciliation in different NIH3T3 sub-cell lines and culture conditions by immunodetection of primary cilia and counting. Quantitative Western blotting, qRT-PCR, and proliferation assays completed our investigation. We observed large differences between NIH3T3 sub-cell lines in their ability to generate acetylated primary cilia that correlated with cytoplasmic tubulin acetylation. We found no increased activity of the major tubulin deacetylase, HDAC6, but instead reduced expression of the α-tubulin acetyltransferase 1 () as being causative. Our observations demonstrate that cells with reduced expression of and tubulin acetylation proliferate faster, eventually displacing all other cells in the population. Expression of and tubulin acetylation are therefore selective forces in cell competition.

摘要

成纤维细胞的伤口愈合反应严重依赖于初级纤毛,这是一种伸向环境的感觉细胞器,包含稳定的轴丝结构。轴丝微管乙酰化是初级纤毛的一个特征性标志。尽管初级纤毛的形成受细胞周期控制,但影响纤毛形成的环境线索尚不完全清楚。因此,我们的目的是研究培养条件对 NIH3T3 成纤维细胞纤毛形成的影响。我们通过免疫检测和计数来量化不同 NIH3T3 亚细胞系和培养条件下的纤毛形成。定量 Western blot、qRT-PCR 和增殖测定完成了我们的研究。我们观察到 NIH3T3 亚细胞系在产生乙酰化初级纤毛的能力上存在很大差异,这与细胞质微管乙酰化相关。我们没有发现主要微管去乙酰化酶 HDAC6 的活性增加,而是发现 α-微管乙酰转移酶 1 () 的表达减少是造成这种情况的原因。我们的观察表明,表达减少和微管乙酰化的细胞增殖更快,最终会取代群体中的所有其他细胞。因此,的表达和微管乙酰化是细胞竞争中的选择力量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50dc/7918103/d29f4db38efd/cells-10-00390-g001.jpg

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