Cited by 337Autophagy in Disease and TherapyAmyotrophic Lateral Sclerosis ResearchAlzheimer's disease research and treatments

Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates

Open access
Korac, Jelena, Schaeffer, Veronique, Kovacevic, Igor, Clement, Albrecht M., Jungblut, Benno, Behl, Christian, Terzic, Janos, Dikic, Ivan·2013·Journal of Cell Science

Abstract

Summary: Aggregation of misfolded proteins and the associated loss of neurons are considered a hallmark of numerous neurodegenerative diseases. Optineurin is present in protein inclusions observed in various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Huntington's disease, Alzheimer's disease, Parkinson's disease, Creutzfeld-Jacob disease and Pick's disease. Optineurin deletion mutations have also been described in ALS patients. However, the role of optineurin in mechanisms of protein aggregation remains unclear. In this report, we demonstrate that optineurin recognizes various protein aggregates via its C-terminal coiled-coil domain in a ubiquitin-independent manner. We also show that optineurin depletion significantly increases protein aggregation in HeLa cells and that morpholino-silencing of the optineurin ortholog in zebrafish causes the motor axonopathy phenotype similar to a zebrafish model of ALS. A more severe phenotype is observed when optineurin is depleted in zebrafish carrying ALS mutations. Furthermore, TANK1 binding kinase 1 (TBK1) is colocalized with optineurin on protein aggregates and is important in clearance of protein aggregates through the autophagy-lysosome pathway. TBK1 phosphorylates optineurin at serine 177 and regulates its ability to interact with autophagy modifiers. This study provides evidence for a ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates as well as additional relevance for TBK1 as an upstream regulator of the autophagic pathway.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1242/jcs.114926

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • OPTN is an autophagy receptor that binds ubiquitinated cargo via its UBAN domain and LC3 via its LIR domain, although it can also act independently of target ubiquitination.

    “OPTN is an autophagy receptor that binds ubiquitinated cargo (via its UBAN domain) and LC3 (via its LIR domain) [194,254,255], although it can also act independently of target ubiquitination [254].”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Korac, J., Schaeffer, V., Kovacevic, I., Clement, A. M., Jungblut, B., Behl, C., Terzic, J., & Dikic, I.
Affiliations
  • Department of Immunology and Medical Genetics, School of Medicine, University of Split, Soltanska 2, 21000 Split, Croatia
  • Institute of Biochemistry II and Buchmann Institute for Molecular Life Sciences, School of Medicine, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt (Main), Germany
  • Johannes Gutenberg University Mainz (DE)
  • Max Planck Institute for Heart and Lung Research (DE)
Venue
Journal of Cell Science
Published
2013-01-15
Volume
126
Issue
2
Pages
580-592
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
OpenAlex
W1985484942
Cited by
336
References
54
Citations by year
2026: 6 · 2025: 21 · 2024: 25 · 2023: 15 · 2022: 25 · 2021: 25 · 2020: 35 · 2019: 31 · 2018: 25 · 2017: 26 · 2016: 35 · 2015: 37 · 2014: 20 · 2013: 10
FWCI
15.99
Type
journal article
Language
en
Open access
Locations
  • Journal of Cell Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
optineurin, TBK1, protein aggregation, autophagy-lysosome pathway, coiled-coil domain, neurodegenerative diseases, amyotrophic lateral sclerosis, zebrafish model, TBK1 phosphorylation, protein inclusions
MeSH terms
Animals, Autophagy, Disease Models, Animal, HeLa Cells, Humans, Mice, Inbred C57BL, Mice, Transgenic, Phosphorylation, Protein Binding, Zebrafish, Cell Cycle Proteins, Neurodegenerative Diseases, Ubiquitin, Membrane Transport Proteins, Transcription Factor TFIIIA, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review