Department of Biology, Section of Cell Biology and Physiology, University of Copenhagen, Copenhagen, Denmark.
Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH, USA.
Nat Rev Nephrol. 2019 Apr;15(4):199-219. doi: 10.1038/s41581-019-0116-9.
Primary cilia project in a single copy from the surface of most vertebrate cell types; they detect and transmit extracellular cues to regulate diverse cellular processes during development and to maintain tissue homeostasis. The sensory capacity of primary cilia relies on the coordinated trafficking and temporal localization of specific receptors and associated signal transduction modules in the cilium. The canonical Hedgehog (HH) pathway, for example, is a bona fide ciliary signalling system that regulates cell fate and self-renewal in development and tissue homeostasis. Specific receptors and associated signal transduction proteins can also localize to primary cilia in a cell type-dependent manner; available evidence suggests that the ciliary constellation of these proteins can temporally change to allow the cell to adapt to specific developmental and homeostatic cues. Consistent with important roles for primary cilia in signalling, mutations that lead to their dysfunction underlie a pleiotropic group of diseases and syndromic disorders termed ciliopathies, which affect many different tissues and organs of the body. In this Review, we highlight central mechanisms by which primary cilia coordinate HH, G protein-coupled receptor, WNT, receptor tyrosine kinase and transforming growth factor-β (TGFβ)/bone morphogenetic protein (BMP) signalling and illustrate how defects in the balanced output of ciliary signalling events are coupled to developmental disorders and disease progression.
初级纤毛从大多数脊椎动物细胞类型的表面呈单拷贝形式伸出；它们可以检测和传递细胞外信号，从而在发育过程中调节各种细胞过程，并维持组织内稳态。初级纤毛的感觉能力依赖于特定受体和相关信号转导模块在纤毛中的协调运输和时间定位。例如，经典的 Hedgehog (HH) 途径是一种真正的纤毛信号系统，它调节发育和组织内稳态中的细胞命运和自我更新。特定的受体和相关信号转导蛋白也可以以细胞类型依赖的方式定位于初级纤毛；现有证据表明，这些蛋白的纤毛排列可以随时间变化，使细胞能够适应特定的发育和内稳态信号。与初级纤毛在信号转导中的重要作用一致，导致其功能障碍的突变是一组称为纤毛病的多系统疾病和综合征的基础，这些疾病和综合征影响身体的许多不同组织和器官。在这篇综述中，我们强调了初级纤毛协调 HH、G 蛋白偶联受体、WNT、受体酪氨酸激酶和转化生长因子-β (TGFβ)/骨形态发生蛋白 (BMP) 信号的核心机制，并说明了纤毛信号事件的平衡输出缺陷如何与发育障碍和疾病进展相关联。
