Primary cilia and signaling pathways in mammalian development, health and disease.
Primary cilia and signaling pathways in mammalian development, health and disease.
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DOI：
10.1159/000208212
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Christensen ST
中科院分区：
文献类型：
--
作者：
Veland IR;Awan A;Pedersen LB;Yoder BK;Christensen ST
虽然初生纤毛最早于1898年被描述，长期以来一直被认为是一个功能不重要的残留细胞器，但它已经成为现代细胞生物学和生理学中最热门的研究课题之一。初级纤毛是大多数生长受阻或分化的哺乳动物细胞表面以单一拷贝形式存在的非运动性感觉细胞器，它们的组装或功能缺陷与许多发育缺陷、疾病和疾病密切相关。在正常组织中，初级纤毛协调一系列信号转导通路，包括Hedgehog、Wnt、PDGFRα和整合素信号转导。在肾脏中，初级纤毛可以作为机械、化学和渗透感觉单位，探测细胞外环境，并通过多囊蛋白向细胞传递信号，而多囊蛋白依赖于纤毛定位来实现适当的功能。事实上，编码纤毛内鞭毛运输(IFT)蛋白的小鼠ift88(以前称为Tg737)基因的亚型突变导致初级纤毛畸形，并在肾小管的集合管中伴随着常染色体隐性遗传性多囊肾病(PKD)的发展。虽然PKD是第一批与初级纤毛功能障碍有关的疾病之一，但该细胞器的缺陷随后与许多其他表型有关，包括癌症、肥胖症、糖尿病以及一些发育缺陷。这些纤毛紊乱统称为纤毛病。在这篇综述中，我们简要概述了初生纤毛的结构和功能，以及它们在哺乳动物发育、健康和疾病中协调信号转导途径中的一些作用。这篇综述是与2008年6月26-27日在巴黎Médecine Necker举行的Takis Anagnostopoulos肾脏和上皮生理学及生理病理学研讨会一起撰写的。
Although first described 1898 and long considered a vestigial organelle of little functional importance, the primary cilium has become one of the hottest research topics in modern cell biology and physiology. Primary cilia are non-motile sensory organelles present in a single copy on the surface of most growth-arrested or differentiated mammalian cells, and defects in their assembly or function are tightly coupled to many developmental defects, diseases and disorders. In normal tissues the primary cilium coordinates a series of signal transduction pathways, including Hedgehog, Wnt, PDGFRα and integrin signaling. In the kidney the primary cilium may function as a mechano-, chemo- and osmosensing unit that probes the extracellular environment and transmits signals to the cell via e.g. polycystins, which depend on ciliary localization for appropriate function. Indeed, hypomorphic mutations in the mouse ift88 (previously called Tg737) gene, which encodes a ciliogenic intraflagellar transport (IFT) protein, result in malformation of primary cilia, and in the collecting ducts of kidney tubules this is accompanied by development of autosomal recessive polycystic kidney disease (PKD). While PKD was one of the first diseases to be linked to dysfunctional primary cilia, defects in this organelle have subsequently been associated with many other phenotypes, including cancer, obesity, diabetes as well as a number of developmental defects. Collectively, these disorders of the cilium are now referred to as the ciliopathies. In this review we provide a brief overview of the structure and function of primary cilia and some of their roles in coordinating signal transduction pathways in mammalian development, health and disease. This review was written in conjunction with the Takis Anagnostopoulos Symposium on Renal and Epithelial Physiology and Physiopathology at Faculté de Médecine Necker in Paris, June 26-27, 2008.
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影响因子：
64.8
作者：
Barr, MM;Sternberg, PW
通讯作者：
Sternberg, PW
影响因子：
15.9
作者：
Chauvet, V;Tian, X;Caplan, MJ
通讯作者：
Caplan, MJ
DOI：
10.1083/jcb.141.4.993
发表时间：
1998-05-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cole DG;Diener DR;Himelblau AL;Beech PL;Fuster JC;Rosenbaum JL
通讯作者：
Rosenbaum JL
DOI：
10.1073/pnas.0804558105
发表时间：
2008-09-02
影响因子：
11.1
作者：
Breunig, Joshua J.;Sarkisian, Matthew R.;Town, Terrence
通讯作者：
Town, Terrence
影响因子：
64.8
作者：
Corbit, KC;Aanstad, P;Reiter, JF
通讯作者：
Reiter, JF