PUBLICATION

The Deubiquitinating Enzyme Ataxin-3 Regulates Ciliogenesis and Phagocytosis in the Retina

Authors
Toulis, V., García-Monclús, S., de la Peña-Ramírez, C., Arenas-Galnares, R., Abril, J.F., Todi, S.V., Khan, N., Garanto, A., Costa, M.D.C., Marfany, G.
ID
ZDB-PUB-201120-94
Date
2020
Source
Cell Reports   33: 108360 (Journal)
Registered Authors
Keywords
ATXN3, HDAC6, KEAP1, Machado-Joseph disease, SCA3, ciliogenesis, photoreceptor, polyglutamine, retinal pigment epithelium phagocytosis, spinocerebellar ataxia
MeSH Terms
  • Animals
  • Ataxin-3/metabolism*
  • Cilia/genetics
  • Cilia/metabolism*
  • Disease Models, Animal
  • Humans
  • Mice
  • Phagocytosis/physiology
  • Retina/metabolism*
  • Transfection
  • Zebrafish
PubMed
33176149 Full text @ Cell Rep.
Abstract
Expansion of a CAG repeat in ATXN3 causes the dominant polyglutamine disease spinocerebellar ataxia type 3 (SCA3), yet the physiological role of ATXN3 remains unclear. Here, we focus on unveiling the function of Ataxin-3 (ATXN3) in the retina, a neurological organ amenable to morphological and physiological studies. Depletion of Atxn3 in zebrafish and mice causes morphological and functional retinal alterations and, more precisely, photoreceptor cilium and outer segment elongation, cone opsin mislocalization, and cone hyperexcitation. ATXN3 localizes at the basal body and axoneme of the cilium, supporting its role in regulating ciliary length. Abrogation of Atxn3 expression causes decreased levels of the regulatory protein KEAP1 in the retina and delayed phagosome maturation in the retinal pigment epithelium. We propose that ATXN3 regulates two relevant biological processes in the retina, namely, ciliogenesis and phagocytosis, by modulating microtubule polymerization and microtubule-dependent retrograde transport, thus positing ATXN3 as a causative or modifier gene in retinal/macular dystrophies.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping