Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Int J Mol Sci. 2022 Oct 19;23(20):12527. doi: 10.3390/ijms232012527.
Proteins related to the ubiquitin-proteasome system play an important role during the differentiation and ciliogenesis of photoreceptor cells. Mutations in several genes involved in ubiquitination and proteostasis have been identified as causative of inherited retinal dystrophies (IRDs) and ciliopathies. USP48 is a deubiquitinating enzyme whose role in the retina is still unexplored although previous studies indicate its relevance for neurosensory organs. In this work, we describe that a pool of endogenous USP48 localises to the basal body in retinal cells and provide data that supports the function of USP48 in the photoreceptor cilium. We also demonstrate that USP48 interacts with the IRD-associated proteins ARL3 and UNC119a, and stabilise their protein levels using different mechanisms. Our results suggest that USP48 may act in the regulation/stabilisation of key ciliary proteins for photoreceptor function, in the modulation of intracellular protein transport, and in ciliary trafficking to the photoreceptor outer segment.
与泛素-蛋白酶体系统相关的蛋白质在光感受器细胞的分化和纤毛发生过程中发挥重要作用。几个参与泛素化和蛋白稳态的基因的突变已被确定为遗传性视网膜营养不良（IRDs）和纤毛病的致病原因。USP48 是一种去泛素化酶，尽管先前的研究表明其与神经感觉器官有关，但它在视网膜中的作用仍未被探索。在这项工作中，我们描述了内源性 USP48 池定位于视网膜细胞的基底体，并提供了支持 USP48 在光感受器纤毛中的功能的数据。我们还表明，USP48 与 IRD 相关蛋白 ARL3 和 UNC119a 相互作用，并使用不同的机制稳定它们的蛋白质水平。我们的结果表明，USP48 可能在调节/稳定关键纤毛蛋白以维持光感受器功能、调节细胞内蛋白质运输以及纤毛向光感受器外节的运输中发挥作用。
