Mutations in the cilium-associated protein CEP290 cause retinal degeneration as part of multiorgan ciliopathies or as retina-specific diseases. The precise location and the functional roles of CEP290 within cilia and, specifically, the connecting cilia (CC) of photoreceptors, remain unclear. We used super-resolution fluorescence microscopy and electron microscopy to localize CEP290 in the CC and in the primary cilia of cultured cells with subdiffraction resolution and to determine effects of CEP290 deficiency in 3 mutant models. Radially, CEP290 localizes in close proximity to the microtubule doublets in the region between the doublets and the ciliary membrane. Longitudinally, it is distributed throughout the length of the CC whereas it is confined to the very base of primary cilia in human retinal pigment epithelium-1 cells. We found Y-shaped links, ciliary substructures between microtubules and membrane, throughout the length of the CC. Severe CEP290 deficiencies in mouse models did not prevent assembly of cilia or cause obvious mislocalization of ciliary components in early stages of degeneration. There were fewer cilia and no normal outer segments in the mutants, but the Y-shaped links were clearly present. These results point to photoreceptor-specific functions of CEP290 essential for CC maturation and stability following the earliest stages of ciliogenesis.
Valencia L. Potter, Abigail R. Moye, Michael A. Robichaux, Theodore G. Wensel
Title and authors | Publication | Year |
---|---|---|
The usherin mutation c.2299delG leads to its mislocalization and disrupts interactions with whirlin and VLGR1
Tebbe L, Mwoyosvi ML, Crane R, Makia MS, Kakakhel M, Cosgrove D, Al-Ubaidi MR, Naash MI |
Nature Communications | 2023 |
Mapping rhodopsin trafficking in rod photoreceptors with quantitative super-resolution microscopy
Haggerty KN, Eshelman SC, Sexton LA, Frimpong E, Rogers LM, Agosto MA, Robichaux MA |
2023 | |
Eupatilin improves cilia defects in human CEP290 ciliopathy models
Corral-Serrano J, Sladen P, Ottaviani D, Rezek F, Jovanovic K, Athanasiou D, van der Spuy J, Mansfield B, Cheetham M |
2023 | |
Extracellular vesicles highlight many cases of photoreceptor degeneration
Spencer WJ |
Frontiers in molecular neuroscience | 2023 |
Comparative analysis of transcriptional changes in zebrafish cep290 and bbs2 mutants by RNA-seq reveals upregulation of inflammatory and stress-related pathways
Grabinski SE, Parsana D, Perkins BD |
Frontiers in molecular neuroscience | 2023 |
Eupatilin Improves Cilia Defects in Human CEP290 Ciliopathy Models
Corral-Serrano JC, Sladen PE, Ottaviani D, Rezek OF, Athanasiou D, Jovanovic K, van der Spuy J, Mansfield BC, Cheetham ME |
Cells | 2023 |
Durable vision improvement after a single intravitreal treatment with antisense oligonucleotide in CEP290-LCA: Replication in two eyes
Cideciyan AV, Jacobson SG, Ho AC, Swider M, Sumaroka A, Roman AJ, Wu V, Russell RC, Viarbitskaya I, Garafalo AV, Schwartz MR, Girach A |
American Journal of Ophthalmology Case Reports | 2023 |
Expansion Microscopy of Mouse Photoreceptor Cilia.
Moyel AR, Robichaux MA, Wensel T |
Advances in experimental medicine and biology | 2023 |
Single-molecule imaging in the primary cilium
Weiss LE, Love JF, Yoon J, Comerci CJ, Milenkovic L, Kanie T, Jackson PK, Stearns T, Gustavsson AK |
Methods in cell biology | 2023 |