Primary cilia biogenesis and associated retinal ciliopathies. (February 2021)

• Record Type: Journal Article
• Authors: Chen, Holly Y.; Kelley, Ryan A.; Li, Tiansen; Swaroop, Anand
• Is Part Of: Seminars in cell & developmental biology. Volume 110(2021)
• Page Start: 70
• Page End: 88
• Publication Date: 2021-02
• Subjects: AAV adeno-associated virus -- AON antisense oligonucleotides -- AV adeno virus -- BB basal body -- BBS Bardet-Biedl syndrome -- CC connecting cilium -- CLS ciliary localization sequence -- Cryo-ET cryo-electron tomography -- CV ciliary vesicle -- DA distal appendage -- DC daughter centriole -- FIB-SEM focused ion beam scanning electron microscopy -- GPCR G protein-coupled receptor -- Hh Hedgehog -- IFT intraflagellar transport -- iPSC induced pluripotent stem cells -- IS inner segment -- JS Joubert syndrome -- JSRD Joubert syndrome and related disorders -- LCA Leber congenital amaurosis -- MC mother centriole -- MEF mouse embryonic fibroblast -- MKS Meckel syndrome -- mTOR mammalian target of Rapamycin -- NPHP nephronophthisis -- OMIM Online Mendelian Inheritance in Man database -- OS outer segment -- PCM pericentriolar material -- PCD primary ciliary dyskinesia -- PCV preciliary vesicle -- PDGFR platelet-derived growth factor receptor -- PTC Premature termination codon -- RP retinitis pigmentosa -- RPE retinal pigment epithelia -- SDA subdistal appendage -- SEM scanning electron microscopy -- sgRNAs single-guide RNAs -- SLS Senior-Løken syndrome -- STED stimulated emission depletion imaging -- STORM super-resolution stochastic optical reconstruction microscopy -- TEM transmission electron microscopy -- TF transition fiber -- TGF transforming growth factor -- TZ transition zone -- Wnt Wingless; Sensory cilia -- Ciliogenesis -- Photoreceptor -- Retinal degeneration -- CEP290 -- Intracellular transport; Cytology -- Periodicals; Developmental biology -- Periodicals; 571.6
• DOI: 10.1016/j.semcdb.2020.07.013
• Languages: English
• ISSNs: 1084-9521

Abstract

Graphical abstract: Abstract: 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.