The Deubiquitinating Enzyme USP48 Interacts with the Retinal Degeneration-Associated Proteins UNC119a and ARL3
Por:
Sánchez-Bellver L, Férriz-Gordillo A, Carrillo-Pz M, Rabanal L, Garcia-Gonzalo FR and Marfany G
Publicada:
1 oct 2022
Ahead of Print:
19 oct 2022
Resumen:
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.
Filiaciones:
Sánchez-Bellver L:
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
Férriz-Gordillo A:
Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain
Carrillo-Pz M:
Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain
Rabanal L:
Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain
Garcia-Gonzalo FR:
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain
Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain
Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas (CSIC), 28029 Madrid, Spain
Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), 28029 Madrid, Spain
Marfany G:
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
Institut de Biomedicina-Institut de Recerca Sant Joan de Déu (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain
DBGen Ocular Genomics, 08028 Barcelona, Spain
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