Atf6-/- mouse photoreceptors exhibit novel ciliary rootlet defect
Bradley, A.; Haggerty, K.; Lee, E.-J.; Robichaux, M. A.; Lin, J. H.
Show abstract
ATF6 is a regulator of the Unfolded Protein Response that maintains cellular homeostasis during ER stress. In patients, ATF6 mutations cause photoreceptor dystrophy and sensorineural hearing loss. Atf6-/- mice develop progressive hearing loss with stereocilia disorganization and mild retinal dysfunction, suggesting that ATF6 loss may impair the structural integrity of sensory cells. To test this possibility, we analyzed the retinal ultrastructure of Atf6-/- mouse photoreceptors using transmission electron microscopy and identified a novel defect in which the ciliary rootlet is unbundled, disorganized, and possibly detached from the basal body. These findings demonstrate that ATF6 is essential for maintaining the structural organization of the photoreceptor ciliary apparatus, linking ER proteostasis to cytoskeletal integrity and providing a potential mechanistic basis for the progressive degeneration of photoreceptor outer segments and stereocilia observed in ATF6-deficient patients.
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