The role of cilia in the pathogenesis of cystic kidney disease.
The role of cilia in the pathogenesis of cystic kidney disease.
复制标题
DOI：
10.1097/mop.0000000000000187
复制
发表时间：
2015-04
影响因子：
3.6
通讯作者：
Dell KM
中科院分区：
文献类型：
--
作者：
Dell KM
初级（不动）纤毛是存在于大多数细胞类型上的特化细胞器。几乎所有与广谱人类囊性肾病相关的蛋白质都定位于纤毛内或周围的区域。异常纤毛结构和/或功能已报道在动物模型和人类囊性肾。这篇综述的目的是讨论目前对异常基因/蛋白质和纤毛相互作用潜在影响肾膀胱形成的机制的理解。新的纤毛钙水平/通道活性的直接记录表明，纤毛形成了一个钙介导的信号微环境，这可能为纤毛特异性的下游信号传递提供了一种机制。遗传学研究证实，纤毛不是囊性肾病发生所必需的，而是通过一种新的、未定义的机制调节囊性肾病的严重程度。纤毛相关蛋白和非纤毛相关蛋白改变纤毛结构/功能的机制也已被确定。在确定异常基因和蛋白质影响纤毛结构和功能的机制方面取得了相当大的进展。然而，这些相互作用导致肾囊肿形成和囊性肾病进展的确切机制尚不清楚。
Primary (immotile) cilia are specialized organelles present on most cell types. Almost all of proteins associated with a broad spectrum of human cystic kidney diseases have been localized to the region in or around the cilia. Abnormal cilia structure and/or function have been reported in animal models and human cystic kidneys. The goal of this review is to discuss current understanding of the mechanisms by which abnormal genes/proteins and cilia interact to potentially influence renal cystogenesis. Novel direct recording of cilia calcium levels/channel activity suggest that cilia form a calcium-mediated signaling microenvironment separate from the cytoplasm, which could provide a mechanism for cilia-specific downstream signaling. Genetic-based studies confirm that cilia are not required for cystogenesis but modulate cystic kidney disease severity through a novel, undefined mechanism. Mechanisms by which both cilia-associated and non-cilia associated proteins can alter cilia structure/function have also been identified. Considerable progress has been made in defining the mechanisms by which abnormal genes and proteins affect cilia structure and function. However, the exact mechanisms by which these interactions cause renal cyst formation and progression of cystic kidney disease are still unknown.