The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates
Open accessAbstract
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.
Overview
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.
Integrity signals
Registry
Cites
Statistics
Verification
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.
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?
In the citing paper
“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].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [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.
Citations
Cites
The zebrafish book : a guide for the laboratory use of zebrafish (Danio rerio)
Westerfield, M. (1995) · Medical Entomology and Zoology · Cited by 6,813
Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578
Motor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H.-X., et al. (1994) · Science · doi:10.1126/science.8209258 · Cited by 4,143
Haine, M. M.-L., & Meeùs, N. (1986) · Cited by 3,464
The Role of Atg Proteins in Autophagosome Formation
Mizushima, N., Yoshimori, T., & Ohsumi, Y. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154005 · Cited by 2,978
Network organization of the human autophagy system
Behrends, C., Sowa, M. E., Gygi, S. P., & Harper, J. W. (2010) · Nature · doi:10.1038/nature09204 · Cited by 1,554
Nix is a selective autophagy receptor for mitochondrial clearance
Novak, I., Kirkin, V., McEwan, D. G., Zhang, J., Wild, P., Rozenknop, A., Rogov, V., Löhr, F., Popovic, D., Occhipinti, A., et al. (2010) · The EMBO Reports · doi:10.1038/embor.2009.256 · Cited by 1,309 · cited 2×
“, 2010), defective mitochondria (Novak et al., 2010) and bacteria Salmonella enterica (Thurston”
BackgroundPhosphorylation of the Autophagy Receptor Optineurin Restricts Salmonella Growth
Wild, P., Farhan, H., McEwan, D. G., Wagner, S., Rogov, V. V., Brady, N. R., Richter, B., Korac, J., Waidmann, O., Choudhary, C., et al. (2011) · Science · doi:10.1126/science.1205405 · Cited by 1,298
A Role for Ubiquitin in Selective Autophagy
Kirkin, V., McEwan, D. G., Novak, I., & Đikić, I. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.04.026 · Cited by 1,268
Mutations of optineurin in amyotrophic lateral sclerosis
Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., Kinoshita, Y., Kamada, M., Nodera, H., Suzuki, H., et al. (2010) · Nature · doi:10.1038/nature08971 · Cited by 1,265
A Role for NBR1 in Autophagosomal Degradation of Ubiquitinated Substrates
Kirkin, V., Lamark, T., Sou, Y.-S., Bjørkøy, G., Nunn, J. L., Bruun, J.-A., Shvets, E., McEwan, D. G., Clausen, T. H., Wild, P., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.01.020 · Cited by 1,065
Cellular strategies for controlling protein aggregation
Tyedmers, J., Mogk, A., & Bukau, B. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2993 · Cited by 921
Thurston, T. L. M., Ryzhakov, G., Bloor, S., von Muhlinen, N., & Randow, F. (2009) · Nature Immunology · doi:10.1038/ni.1800 · Cited by 901
Ubiquitin-Binding Proteins: Decoders of Ubiquitin-Mediated Cellular Functions
Husnjak, K., & Đikić, I. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-051810-094654 · Cited by 794
Protein aggregation diseases: pathogenicity and therapeutic perspectives
Aguzzi, A., & O’Connor, T. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3050 · Cited by 766
Allen, B., Ingram, E., Takao, M., Smith, M. J., Jakes, R., Virdee, K., Yoshida, H., Holzer, M., Craxton, M., Emson, P. C., et al. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-21-09340.2002 · Cited by 763
Pankiv, S., Alemu, E. A., Brech, A., Bruun, J., Lamark, T., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200907015 · Cited by 684
Selective autophagy: ubiquitin-mediated recognition and beyond
Kraft, C., Peter, M., & Hofmann, K. (2010) · Nature Cell Biology · doi:10.1038/ncb0910-836 · Cited by 639
The regulation of autophagy – unanswered questions
Chen, Y., & Klionsky, D. J. (2010) · Journal of Cell Science · doi:10.1242/jcs.064576 · Cited by 617
Mechanisms of cross‐talk between the ubiquitin‐proteasome and autophagy‐lysosome systems
Korolchuk, V. I., Menzies, F. M., & Rubinsztein, D. C. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.12.047 · Cited by 581
Filimonenko, M., Isakson, P., Finley, K. D., Anderson, M. R., Jeong, H., Melia, T. J., Bartlett, B. J., Myers, K. M., Birkeland, H. C. G., Lamark, T., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.04.007 · Cited by 449
Optineurin links myosin VI to the Golgi complex and is involved in Golgi organization and exocytosis
Sahlender, D. A., Roberts, R. C., Arden, S. D., Spudich, G. M., Taylor, M. J., Luzio, J. P., Kendrick‐Jones, J., & Buß, F. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200501162 · Cited by 426
BAG3 mediates chaperone‐based aggresome‐targeting and selective autophagy of misfolded proteins
Gamerdinger, M., Kaya, A. M., Uwe Wolfrum, B., Clement, A. M., & Behl, C. (2011) · EMBO Reports · doi:10.1038/embor.2010.203 · Cited by 362
Self-citationAlbagha, O., Visconti, M. R., Alonso, N., Langston, A. L., Cundy, T., Dargie, R., Dunlop, M. G., Fraser, W. D., Hooper, M. J., Isaia, G., et al. (2010) · Nature Genetics · doi:10.1038/ng.562 · Cited by 287
Zhu, G., Wu, C.-J., Zhao, Y., & Ashwell, J. D. (2007) · Current Biology · doi:10.1016/j.cub.2007.07.041 · Cited by 282
FIP-2, a coiled-coil protein, links Huntingtin to Rab8 and modulates cellular morphogenesis
Hattula, K., & Peränen, J. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00864-2 · Cited by 233
Ubiquitin binding mediates the NF-κB inhibitory potential of ABIN proteins
Wagner, S., Carpentier, I., Rogov, V. V., Kreike, M., Ikeda, F., Löhr, F., Wu, C.-J., Ashwell, J. D., Dötsch, V., Đikić, I., et al. (2008) · Oncogene · doi:10.1038/sj.onc.1211042 · Cited by 223
Selective Autophagy in Cancer Development and Therapy
Đikić, I., Johansen, T., & Kirkin, V. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4027 · Cited by 217
Modeling Neurodegeneration in Zebrafish
Xi, Y., Noble, S., & Ekker, M. (2011) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-011-0182-2 · Cited by 211
Sequestosome 1/p62 links familial ALS mutant SOD1 to LC3 via an ubiquitin‐independent mechanism
Gal, J., Ström, A., Kwinter, D. M., Kilty, R., Zhang, J., Shi, P., Fu, W., Wooten, M. W., & Zhu, H. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06388.x · Cited by 187
del Toro, D., Alberch, J., Lázaro‐Diéguez, F., Martín‐Ibáñez, R., Xifró, X., Egea, G., & Canals, J. M. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-07-0726 · Cited by 185
Progranulin is Neurotrophic In Vivo and Protects against a Mutant TDP-43 Induced Axonopathy
Laird, A. S., Hoecke, A. V., Muynck, L. D., Timmers, M., Bosch, L. V. D., Damme, P. V., & Robberecht, W. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013368 · Cited by 154
Overexpression of mutant superoxide dismutase 1 causes a motor axonopathy in the zebrafish
Lemmens, R., Hoecke, A. V., Hersmus, N., Geelen, V., Dhollander, I., Thijs, V., Bosch, L. V. D., Carmeliet, P., & Robberecht, W. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm193 · Cited by 151
Inhibition of Metabotropic Glutamate Receptor Signaling by the Huntingtin-binding Protein Optineurin
Anborgh, P. H., Godin, C. M., Pampillo, M., Dhami, G. K., Dale, L. B., Cregan, S. P., Truant, R., & Ferguson, S. S. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504508200 · Cited by 141
Optineurin in neurodegenerative diseases
Osawa, T., Mizuno, Y., Fujita, Y., Takatama, M., Nakazato, Y., & Okamoto, K. (2011) · Neuropathology · doi:10.1111/j.1440-1789.2011.01199.x · Cited by 128
Involvement of the ubiquitin‐like domain of TBK1/IKK‐i kinases in regulation of IFN‐inducible genes
Ikeda, F., Hecker, C., Rozenknop, A., Nordmeier, R. D., Rogov, V. V., Hofmann, K., Akira, S., Dötsch, V., & Đikić, I. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601773 · Cited by 127
Current status of SOD1 mutations in familial amyotrophic lateral sclerosis
Gaudette, M. (2000) · Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders · doi:10.1080/14660820050515377 · Cited by 114
Novel optineurin mutations in patients with familial and sporadic amyotrophic lateral sclerosis
Bo, R. D., Tiloca, C., Pensato, V., Corrado, L., Ratti, A., Ticozzi, N., Corti, S. P., Castellotti, B., Mazzini, L., Sorarú, G., et al. (2011) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2011.242313 · Cited by 104
p62/SQSTM1 in autophagic clearance of a non-ubiquitylated substrate
Watanabe, Y., & Tanaka, M. (2011) · Journal of Cell Science · doi:10.1242/jcs.081232 · Cited by 103
Kachaner, D., Filipe, J. C.-R., Laplantine, E., Bauch, A., Bennett, K. L., Superti‐Furga, G., Israël, A., & Weil, R. (2012) · Molecular Cell · doi:10.1016/j.molcel.2011.12.030 · Cited by 89
The small heat shock proteins αB-crystallin and Hsp27 suppress SOD1 aggregation in vitro
Yerbury, J. J., Gower, D., Vanags, L. Z., Roberts, K., Lee, J., & Ecroyd, H. W. (2012) · Cell Stress and Chaperones · doi:10.1007/s12192-012-0371-1 · Cited by 85
Hortobágyi, T., Troakes, C., Nishimura, A. L., Vance, C. A., Swieten, J. C. V., Seelaar, H., King, A., Al‐Sarraj, S., Rogelj, B., & Shaw, C. E. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0813-3 · Cited by 83
Witan, H., Kern, A., Koziollek‐Drechsler, I., Wade, R. C., Behl, C., & Clement, A. M. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn025 · Cited by 78
Self-citationOptineurin in primary open angle glaucoma
Sarfarazi, M., & Rezaie, T. (2003) · Ophthalmology Clinics of North America · doi:10.1016/s0896-1549(03)00061-0 · Cited by 69
Novel optineurin mutations in sporadic amyotrophic lateral sclerosis patients
van Blitterswijk, M., van Vught, P. W. J., van Es, M. A., Schelhaas, H. J., van der Kooi, A. J., de Visser, M., Veldink, J. H., & van den Berg, L. H. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.05.019 · Cited by 67
Deng, H.-X. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.178 · Cited by 67
Ito, H., Fujita, K., Nakamura, M., Wate, R., Kaneko, S., Sasaki, S., Yamane, K., Suzuki, N., Aoki, M., Shibata, N., et al. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0809-z · Cited by 63
Optineurin and Its Mutants: Molecules Associated with Some Forms of Glaucoma
Chalasani, M. L. S., Swarup, G., & Balasubramanian, D. (2009) · Ophthalmic Research · doi:10.1159/000232400 · Cited by 57
Chung, P. Y. J., Beyens, G., Boonen, S., Papapoulos, S. E., Geusens, P., Karperien, M., Vanhoenacker, F. M. H. M., Verbruggen, L., Fransén, E., Offel, J. V., et al. (2010) · Human Genetics · doi:10.1007/s00439-010-0888-2 · Cited by 57
A novel heterozygous nonsense mutation of the OPTN gene segregating in a Danish family with ALS
Tümer, Z., Bertelsen, B., Gredal, O., Magyari, M., Nielsen, K. C., LuCamp, Grønskov, K., & Brøndum‐Nielsen, K. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.07.001 · Cited by 51
Novel deletion mutations of OPTN in amyotrophic lateral sclerosis in Japanese
Iida, A., Hosono, N., Sano, M., Kamei, T., Oshima, S., Tokuda, T., Nakajima, M., Kubo, M., Nakamura, Y., & Ikegawa, S. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.12.037 · Cited by 50
Optineurin in Huntington's disease intranuclear inclusions
Schwab, C., Yu, S. Y., McGeer, E. G., & McGeer, P. L. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.10.070 · Cited by 46
Screening for OPTN mutations in amyotrophic lateral sclerosis in a mainly Caucasian population
Sugihara, K., Maruyama, H., Kamada, M., Morino, H., & Kawakami, H. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.03.024 · Cited by 26
Modeling Neurodegenerative Diseases in Zebrafish Embryos
Laird, A. S., & Robberecht, W. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-328-8_11 · Cited by 14
Cited by
Sorted by citations
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citationThe role of autophagy in neurodegenerative disease
Nixon, R. A. (2013) · Nature Medicine · doi:10.1038/nm.3232 · Cited by 2,059
Molecular definitions of autophagy and related processes
Galluzzi, L., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cecconi, F., Choi, A. M., Chu, C. T., Codogno, P., Colombo, M. I., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201796697 · Cited by 1,646
Rogov, V., Dötsch, V., Johansen, T., & Kirkin, V. (2014) · Molecular Cell · doi:10.1016/j.molcel.2013.12.014 · Cited by 992
Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways
Cirulli, E. T., Lasseigne, B. N., Petrovski, S., Sapp, P. C., Dion, P. A., Leblond, C. S., Couthouis, J., Lu, Y.-F., Wang, Q., Krueger, B. J., et al. (2015) · Science · doi:10.1126/science.aaa3650 · Cited by 966
Metadata
- 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
- Publisher
- The Company of Biologists
- Published
- 2013-01-15
- Volume
- 126
- Issue
- 2
- Pages
- 580-592
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- PMC
- PMC3654196
- 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
- green
- europepmc.org
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
