Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Semin Cell Dev Biol. 2021 Feb;110:70-88. doi: 10.1016/j.semcdb.2020.07.013. Epub 2020 Jul 31.
The primary cilium is a ubiquitous microtubule-based organelle that senses external environment and modulates diverse signaling pathways in different cell types and tissues. The cilium originates from the mother centriole through a complex set of cellular events requiring hundreds of distinct components. Aberrant ciliogenesis or ciliary transport leads to a broad spectrum of clinical entities with overlapping yet highly variable phenotypes, collectively called ciliopathies, which include sensory defects and syndromic disorders with multi-organ pathologies. For efficient light detection, photoreceptors in the retina elaborate a modified cilium known as the outer segment, which is packed with membranous discs enriched for components of the phototransduction machinery. Retinopathy phenotype involves dysfunction and/or degeneration of the light sensing photoreceptors and is highly penetrant in ciliopathies. This review will discuss primary cilia biogenesis and ciliopathies, with a focus on the retina, and the role of CP110-CEP290-CC2D2A network. We will also explore how recent technologies can advance our understanding of cilia biology and discuss new paradigms for developing potential therapies of retinal ciliopathies.
纤毛是一种普遍存在的微管细胞器，能够感知外部环境，并在不同类型的细胞和组织中调节多种信号通路。纤毛由母中心粒通过一系列复杂的细胞事件起源，这些事件需要数百种不同的成分。纤毛发生异常或纤毛运输异常会导致广泛的临床实体，具有重叠但高度可变的表型，统称为纤毛病，包括感觉缺陷和多器官病变的综合征障碍。为了有效探测光线，视网膜中的光感受器会形成一种称为外节的改良纤毛，外节充满了富含光转导机制成分的膜盘。视网膜病变表型涉及感光光感受器的功能障碍和/或退化，在纤毛病中高度普遍。本文将讨论原发性纤毛生物发生和纤毛病，重点是视网膜以及 CP110-CEP290-CC2D2A 网络的作用。我们还将探讨最近的技术如何提高我们对纤毛生物学的理解，并讨论开发视网膜纤毛病潜在治疗方法的新范例。
