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分裂细胞中纤毛发生抑制的机制。

Mechanisms of ciliogenesis suppression in dividing cells.

作者信息

Goto Hidemasa, Inaba Hironori, Inagaki Masaki

机构信息

Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, 464-8681, Japan.

Department of Cellular Oncology, Graduate School of Medicine, Nagoya University, Nagoya, 466-8550, Japan.

出版信息

Cell Mol Life Sci. 2017 Mar;74(5):881-890. doi: 10.1007/s00018-016-2369-9. Epub 2016 Sep 26.

Abstract

The primary cilium is a non-motile and microtubule-enriched protrusion ensheathed by plasma membrane. Primary cilia function as mechano/chemosensors and signaling hubs and their disorders predispose to a wide spectrum of human diseases. Most types of cells assemble their primary cilia in response to cellular quiescence, whereas they start to retract the primary cilia upon cell-cycle reentry. The retardation of ciliary resorption process has been shown to delay cell-cycle progression to the S or M phase after cell-cycle reentry. Apart from this conventional concept of ciliary disassembly linked to cell-cycle reentry, recent studies have led to a novel concept, suggesting that cells can suppress primary cilia assembly during cell proliferation. Accumulating evidence has also demonstrated the importance of Aurora-A (a protein originally identified as one of mitotic kinases) not only in ciliary resorption after cell-cycle reentry but also in the suppression of ciliogenesis in proliferating cells, whereas Aurora-A activators are clearly distinct in both phenomena. Here, we summarize the current knowledge of how cycling cells suppress ciliogenesis and compare it with mechanisms underlying ciliary resorption after cell-cycle reentry. We also discuss a reciprocal relationship between primary cilia and cell proliferation.

摘要

初级纤毛是一种由质膜包裹的、富含微管的非运动性突出物。初级纤毛作为机械/化学传感器和信号枢纽,其功能紊乱易引发多种人类疾病。大多数细胞类型在细胞静止时组装初级纤毛,而在细胞周期重新进入时开始回缩初级纤毛。已证明纤毛吸收过程的延迟会在细胞周期重新进入后延迟细胞周期进入S期或M期。除了这种与细胞周期重新进入相关的纤毛解聚的传统概念外,最近的研究还提出了一个新的概念,即细胞在增殖过程中可以抑制初级纤毛的组装。越来越多的证据还表明,极光激酶A(一种最初被鉴定为有丝分裂激酶之一的蛋白质)不仅在细胞周期重新进入后的纤毛吸收中起重要作用,而且在抑制增殖细胞中的纤毛发生中也起重要作用,而极光激酶A激活剂在这两种现象中明显不同。在这里,我们总结了目前关于循环细胞如何抑制纤毛发生的知识,并将其与细胞周期重新进入后纤毛吸收的机制进行比较。我们还讨论了初级纤毛与细胞增殖之间的相互关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f710/11107547/a85ffe78d9c7/18_2016_2369_Fig1_HTML.jpg

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