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纤毛长度控制的细胞机制

Cellular Mechanisms of Ciliary Length Control.

作者信息

Keeling Jacob, Tsiokas Leonidas, Maskey Dipak

机构信息

Department of Cell Biology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, OK 73104, USA.

出版信息

Cells. 2016 Jan 29;5(1):6. doi: 10.3390/cells5010006.

DOI:10.3390/cells5010006
PMID:26840332
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4810091/
Abstract

Cilia and flagella are evolutionarily conserved, membrane-bound, microtubule-based organelles on the surface of most eukaryotic cells. They play important roles in coordinating a variety of signaling pathways during growth, development, cell mobility, and tissue homeostasis. Defects in ciliary structure or function are associated with multiple human disorders called ciliopathies. These diseases affect diverse tissues, including, but not limited to the eyes, kidneys, brain, and lungs. Many processes must be coordinated simultaneously in order to initiate ciliogenesis. These include cell cycle, vesicular trafficking, and axonemal extension. Centrioles play a central role in both cell cycle progression and ciliogenesis, making the transition between basal bodies and mitotic spindle organizers integral to both processes. The maturation of centrioles involves a functional shift from cell division toward cilium nucleation which takes place concurrently with its migration and fusion to the plasma membrane. Several proteinaceous structures of the distal appendages in mother centrioles are required for this docking process. Ciliary assembly and maintenance requires a precise balance between two indispensable processes; so called assembly and disassembly. The interplay between them determines the length of the resulting cilia. These processes require a highly conserved transport system to provide the necessary substances at the tips of the cilia and to recycle ciliary turnover products to the base using a based microtubule intraflagellar transport (IFT) system. In this review; we discuss the stages of ciliogenesis as well as mechanisms controlling the lengths of assembled cilia.

摘要

纤毛和鞭毛是大多数真核细胞表面进化上保守的、膜结合的、基于微管的细胞器。它们在生长、发育、细胞迁移和组织稳态过程中协调多种信号通路发挥重要作用。纤毛结构或功能的缺陷与多种称为纤毛病的人类疾病相关。这些疾病影响多种组织,包括但不限于眼睛、肾脏、大脑和肺部。为了启动纤毛发生,许多过程必须同时协调进行。这些过程包括细胞周期、囊泡运输和轴丝延伸。中心粒在细胞周期进程和纤毛发生中都起着核心作用,使得基体和有丝分裂纺锤体组织者之间的转变对这两个过程都不可或缺。中心粒的成熟涉及从细胞分裂向纤毛成核的功能转变,这与它向质膜的迁移和融合同时发生。母中心粒远端附属物的几种蛋白质结构是这种对接过程所必需的。纤毛组装和维持需要两个不可或缺的过程之间精确平衡,即所谓的组装和拆卸。它们之间的相互作用决定了最终纤毛的长度。这些过程需要一个高度保守的运输系统,以在纤毛尖端提供必要的物质,并使用基于微管的鞭毛内运输(IFT)系统将纤毛周转产物循环回基部。在这篇综述中,我们讨论了纤毛发生的阶段以及控制组装后纤毛长度的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61fb/4810091/72699a89e40e/cells-05-00006-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61fb/4810091/0832053c1125/cells-05-00006-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61fb/4810091/72699a89e40e/cells-05-00006-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61fb/4810091/0832053c1125/cells-05-00006-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61fb/4810091/72699a89e40e/cells-05-00006-g002.jpg

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本文引用的文献

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J Cell Biol. 2015 Dec 7;211(5):963-73. doi: 10.1083/jcb.201502043.
2
Intraflagellar transport is essential for mammalian spermiogenesis but is absent in mature sperm.鞭毛内运输对于哺乳动物精子发生至关重要,但在成熟精子中不存在。
Mol Biol Cell. 2015 Dec 1;26(24):4358-72. doi: 10.1091/mbc.E15-08-0578. Epub 2015 Sep 30.
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Cell cycle-dependent ubiquitylation and destruction of NDE1 by CDK5-FBW7 regulates ciliary length.
脊椎动物运动性纤毛远端末梢的分子组织
bioRxiv. 2025 Feb 19:2025.02.19.639145. doi: 10.1101/2025.02.19.639145.
4
Somatostatin triggers local cAMP and Ca signaling in primary cilia to modulate pancreatic β-cell function.生长抑素触发初级纤毛中的局部环磷酸腺苷(cAMP)和钙信号传导,以调节胰腺β细胞功能。
EMBO J. 2025 Mar;44(6):1663-1691. doi: 10.1038/s44318-025-00383-7. Epub 2025 Feb 12.
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A network of interacting ciliary tip proteins with opposing activities imparts slow and processive microtubule growth.一个由具有相反活性的相互作用的纤毛尖端蛋白组成的网络赋予微管缓慢且持续的生长。
Nat Struct Mol Biol. 2025 Jan 24. doi: 10.1038/s41594-025-01483-y.
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