Primary cilia and the cell cycle.

Primary cilia and the cell cycle.
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DOI:
10.1016/s0091-679x(08)94007-3
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发表时间:
2009
影响因子:
--
通讯作者:
Golemis, Erica A.
Golemis, Erica A.
中科院分区:
生物学4区
文献类型:
--
作者:
Plotnikova, Olga V.;Pugacheva, Elena N.;Golemis, Erica A.

文献摘要

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纤毛是从细胞表面突出的基于微管的结构,并且充当调节细胞分化或分裂的机械和化学环境线索的传感器。在后生动物中,纤毛信号传导在生物体发育和成体组织的稳态控制中都是重要的,Hedgehog、PDGF、Wnt和其他信号传导级联的受体沿纤毛膜排列并活跃沿着。在正常细胞中,纤毛在细胞周期进程中受到动态调节:存在于G 0和G1细胞中,通常存在于S/G2细胞中,但几乎总是在有丝分裂进入前被吸收,在胞质分裂后重新出现。纤毛的这种周期性的再吸收和重新组装,通过与内在细胞周期机制的相互作用来指定,影响细胞对纤毛相关受体的外在信号影响的易感性。与纤毛完整性的丧失或缺陷相关的哺乳动物的致病性病症包括许多发育障碍、成人囊性综合征和一些癌症。随着与纤毛异常相关的人类疾病列表的持续扩展,鉴定调节纤毛生长和拆卸的细胞机制已成为强烈研究兴趣的主题。虽然这些机制还远未被理解,但最近的一些研究已经开始确定可能开始为疾病发病机制和治疗提供见解的关键调节因子。在这一章中,我们将讨论目前的知识状态关于细胞周期控制的纤毛动力学,并提供一般的方法,可以应用于调查细胞周期依赖的纤毛生长和拆卸。
Cilia are microtubule-based structures that protrude from the cell surface, and function as sensors for mechanical and chemical environmental cues that regulate cellular differentiation or division. In metazoans, ciliary signaling is important both during organismal development and in the homeostasis controls of adult tissues, with receptors for the Hedgehog, PDGF, Wnt, and other signaling cascades arrayed and active along the ciliary membrane. In normal cells, cilia are dynamically regulated during cell cycle progression: present in G0 and G1 cells, and usually in S/G2 cells, but almost invariably resorbed before mitotic entry, to re-appear post-cytokinesis. This periodic resorption and reassembly of cilia, specified by interaction with the intrinsic cell cycle machinery, influences the susceptibility of cells to the influence of extrinsic signals with cilia-associated receptors. Pathogenic conditions of mammals associated with loss of or defects in ciliary integrity include a number of developmental disorders, cystic syndromes in adults, and some cancers. With the continuing expansion of the list of human diseases associated with ciliary abnormalities, the identification of the cellular mechanisms regulating ciliary growth and disassembly has become a topic of intense research interest. Although these mechanisms are far from being understood, a number of recent studies have begun to identify key regulatory factors that may begin to offer insight into disease pathogenesis and treatment. In this chapter we will discuss the current state of knowledge regarding cell cycle control of ciliary dynamics, and provide general methods that can be applied to investigate cell cycle-dependent ciliary growth and disassembly.