The Deubiquitinating Enzyme Ataxin-3 Regulates Ciliogenesis and Phagocytosis in the Retina.
ATXN3
HDAC6
KEAP1
Machado-Joseph disease
SCA3
ciliogenesis
photoreceptor
polyglutamine
retinal pigment epithelium phagocytosis
spinocerebellar ataxia
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
10 11 2020
10 11 2020
Historique:
received:
13
01
2020
revised:
04
09
2020
accepted:
17
10
2020
entrez:
11
11
2020
pubmed:
12
11
2020
medline:
16
11
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33176149
pii: S2211-1247(20)31349-8
doi: 10.1016/j.celrep.2020.108360
pmc: PMC8738964
mid: NIHMS1762177
pii:
doi:
Substances chimiques
Ataxin-3
EC 3.4.19.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108360Subventions
Organisme : NINDS NIH HHS
ID : R01 NS086778
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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