The DOI matches its Crossref record; 74 of the 75 references it cites were found in a registry or an index.
The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy
Open accessAbstract
A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). C9orf72 encodes two C9orf72 protein isoforms of unclear function. Reduced levels of C9orf72 expression have been reported in C9ALS/FTD patients, and although C9orf72 haploinsufficiency has been proposed to contribute to C9ALS/FTD, its significance is not yet clear. Here, we report that C9orf72 interacts with Rab1a and the Unc‐51‐like kinase 1 (ULK1) autophagy initiation complex. As a Rab1a effector, C9orf72 controls initiation of autophagy by regulating the Rab1a‐dependent trafficking of the ULK1 autophagy initiation complex to the phagophore. Accordingly, reduction of C9orf72 expression in cell lines and primary neurons attenuated autophagy and caused accumulation of p62‐positive puncta reminiscent of the p62 pathology observed in C9ALS/FTD patients. Finally, basal levels of autophagy were markedly reduced in C9ALS/FTD patient‐derived iNeurons. Thus, our data identify C9orf72 as a novel Rab1a effector in the regulation of autophagy and indicate that C9orf72 haploinsufficiency and associated reductions in autophagy might be the underlying cause of C9ALS/FTD‐associated p62 pathology. C9ALS/FTD‐associated C9orf72 is a Rab1a effector that controls initiation of autophagy by regulating ULK1 complex trafficking. Disruption of C9orf72 function inhibits autophagy and mimics the p62 pathology found in C9ALS/FTD patients. C9ALS/FTD iNeurons display reduced autophagy. ALS/FTD‐associated C9orf72 is a Rab1a effector that controls initiation of autophagy by regulating ULK1 complex trafficking.
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
“Additionally, through its interactions with ULK1 and RAB1A, a GTP-binding protein involved in vesicular protein trafficking and MTOR regulation [151,152], C9orf72 promotes autophagy initiation [153].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [153]
In the citing paper
“C9orf72 mutations are associated with reduced basal autophagy and enhanced sensitivity to autophagy inhibitors in human iPSC-derived neurons [153,178].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [153]
In the citing paper
“Because wild‐type C9orf72 is involved in central aspects of autophagosomes formation, maturation, and trafficking, it is likely that perturbations in autophagy contribute to the detrimental action of mutated C9orf72 in motor neuron dysfunction (Webster et al, 2016; Ho et al, 2019).”
From Autophagy in major human diseases (2021) · cites this paper as Webster et al, 2016
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
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351
Abràmoff, M. D., Magalhães, P. J., & Ram, S. J. (2004) · Utrecht University Repository (Utrecht University) · Cited by 11,816
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227
Cui, C., Cui, J., Jin, F., Cui, Y., Li, R., Jiang, X., Tian, Y., Wang, R. C., Jiang, P., & Gao, J. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479571 · Cited by 5,214
DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.011 · Cited by 4,936 · cited 5×
“Alternative splicing of C9orf72 is predicted to yield three mRNAs that code for two C9orf72 isoforms, a 481 amino acid (aa) isoform of approximately 50 kDa, C9orf72L (aa 1 – 481) and a 222 aa, 25 kDa isoform, C9orf72S (aa 1 – 221), respectively (DeJesus-Hernandez et al , 2011).”
InfluentialPankiv, 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
A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD
Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.010 · Cited by 4,409
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882
Antimicrobial Autophagy: A Conserved Innate Immune Response in Drosophila
Moy, R. H., & Cherry, S. R. (2013) · Journal of Innate Immunity · doi:10.1159/000350326 · Cited by 3,551
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500
Cited by
Sorted by citations
Mechanism and medical implications of mammalian autophagy
Dikic, I., & Elazar, Z. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0003-4 · Cited by 2,771
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-citationHardiman, O. M., Al‐Chalabi, A., Chiò, A., Corr, E. M., Logroscino, G., Robberecht, W., Shaw, P. J., Simmons, Z., & van den Berg, L. H. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.71 · Cited by 2,262
Self-citationDecoding ALS: from genes to mechanism
Taylor, J. P., Brown, R. H., & Cleveland, D. W. (2016) · Nature · doi:10.1038/nature20413 · Cited by 2,120
Autophagy in major human diseases
Klionsky, D. J., Petroni, G., Amaravadi, R. K., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cadwell, K., Cecconi, F., Choi, A. M. K., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108863 · Cited by 1,585
Amyotrophic lateral sclerosis: a clinical review
Masrori, P., & Damme, P. V. (2020) · European Journal of Neurology · doi:10.1111/ene.14393 · Cited by 1,315
Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities
Menzies, F. M., Fleming, A., Caricasole, A., Bento, C. F., Andrews, S. P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez Sanchez, M., Karabiyik, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.022 · Cited by 1,134
The lysosome as a cellular centre for signalling, metabolism and quality control
Lawrence, R. E., & Zoncu, R. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0244-7 · Cited by 920
Lamptey, R. N. L., Chaulagain, B., Trivedi, R., Gothwal, A., Layek, B., & Singh, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031851 · Cited by 1,010
The mammalian ULK1 complex and autophagy initiation
Zachari, M., & Ganley, I. G. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170021 · Cited by 789
C9orf72-mediated ALS and FTD: multiple pathways to disease
Balendra, R., & Isaacs, A. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0047-2 · Cited by 715
Mechanisms of Autophagy Initiation
Hurley, J. H., & Young, L. N. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044820 · Cited by 681
Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons
Shi, Y., Lin, S., Staats, K. A., Li, Y., Chang, W.-H., Hung, S.-T., Hendricks, E., Linares, G. R., Wang, Y., Son, E. Y., et al. (2018) · Nature Medicine · doi:10.1038/nm.4490 · Cited by 566
The role of mitochondria in amyotrophic lateral sclerosis
Smith, E. F., Shaw, P. J., & Vos, K. J. D. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.06.052 · Cited by 579
Self-citationMead, R. J., Shan, N., Reiser, H. J., Marshall, F., & Shaw, P. J. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00612-2 · Cited by 505
Self-citationThe different autophagy degradation pathways and neurodegeneration
Fleming, A., Bourdenx, M., Fujimaki, M., Karabiyik, C., Krause, G. J., Lopez, A., Martín‐Segura, A., Puri, C., Scrivo, A., Skidmore, J., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.01.017 · Cited by 500
Immune dysregulation in amyotrophic lateral sclerosis: mechanisms and emerging therapies
Beers, D. R., & Appel, S. H. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30394-6 · Cited by 396
Autophagy: An Essential Degradation Program for Cellular Homeostasis and Life
Chun, Y., & Kim, J. (2018) · Cells · doi:10.3390/cells7120278 · Cited by 396
ALS Genetics: Gains, Losses, and Implications for Future Therapies
Kim, G., Gautier, O., Tassoni-Tsuchida, E., Ma, X. R., & Gitler, A. D. (2020) · Neuron · doi:10.1016/j.neuron.2020.08.022 · Cited by 370
Autophagosome biogenesis: From membrane growth to closure
Melia, T. J., Lystad, A. H., & Simonsen, A. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.202002085 · Cited by 340
A molecular perspective of mammalian autophagosome biogenesis
Mercer, T. J., Gubaš, A., & Tooze, S. A. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.810366 · Cited by 275
Autophagy, aging, and age-related neurodegeneration
Palmer, J. E., Wilson, N., Son, S. M., Obrocki, P., Wróbel, L., Rob, M., Takla, M., Korolchuk, V. I., & Rubinsztein, D. C. (2024) · Neuron · doi:10.1016/j.neuron.2024.09.015 · Cited by 277
A C9ORF72/SMCR8-containing complex regulates ULK1 and plays a dual role in autophagy
Yang, M., Liang, C., Swaminathan, K., Herrlinger, S., Lai, F., Shiekhattar, R., & Chen, J.-F. (2016) · Science Advances · doi:10.1126/sciadv.1601167 · Cited by 238
Rab GTPases and Membrane Trafficking in Neurodegeneration
Kiral, F. R., Kohrs, F. E., Jin, E. J., & Hiesinger, P. R. (2018) · Current Biology · doi:10.1016/j.cub.2018.02.010 · Cited by 249
Vos, K. J. D., & Hafezparast, M. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.02.004 · Cited by 238
Zhu, Q., Jiang, J., Gendron, T. F., McAlonis-Downes, M., Jiang, L., Taylor, A., Diaz Garcia, S., Ghosh Dastidar, S., Rodriguez, M. J., King, P., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0619-5 · Cited by 220
Gao, F., Almeida, S., & Lopez‐Gonzalez, R. (2017) · The EMBO Journal · doi:10.15252/embj.201797568 · Cited by 227
Heterochromatin anomalies and double-stranded RNA accumulation underlie C9orf72 poly(PR) toxicity
Zhang, Y., Guo, L. E., Gonzales, P. K., Gendron, T. F., Wu, Y., Jansen‐West, K. R., O’Raw, A. D., Pickles, S. R., Prudencio, M., Carlomagno, Y., et al. (2019) · Science · doi:10.1126/science.aav2606 · Cited by 211
Modelling amyotrophic lateral sclerosis: progress and possibilities
Damme, P. V., Robberecht, W., & Bosch, L. V. D. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.029058 · Cited by 225
Cortés, C. J., & Spada, A. R. L. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.05.012 · Cited by 199
Loss of C9orf72 Enhances Autophagic Activity via Deregulated mTOR and TFEB Signaling
Ugolino, J., Ji, Y. J., Conchina, K., Chu, J., Nirujogi, R. S., Pandey, A., Brady, N. R., Hamacher-Brady, A., & Wang, J. (2016) · PLOS Genetics · doi:10.1371/journal.pgen.1006443 · Cited by 185
Varcianna, A., Myszczynska, M. A., Castelli, L. M., O'Neill, B., Kim, Y., Talbot, J., Nyberg, S., Nyamali, I., Heath, P. R., Stopford, M. J., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2018.11.067 · Cited by 194
Self-citationDistinct roles for motor neuron autophagy early and late in the SOD1 G93A mouse model of ALS
Rudnick, N. D., Griffey, C. J., Guarnieri, P., Gerbino, V., Wang, X., Piersaint, J. A., Tapia, J. C., Rich, M. M., & Maniatis, T. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1704294114 · Cited by 189
Autophagy and ALS: mechanistic insights and therapeutic implications
Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189
Autophagy-Independent Lysosomal Targeting Regulated by ULK1/2-FIP200 and ATG9
Goodwin, J. M., Dowdle, W. E., DeJesus, R., Wang, Z., Bergman, P., Kobylarz, M. J., Lindeman, A., Xavier, R. J., McAllister, G., Nyfeler, B., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.034 · Cited by 189
Autophagic and endo-lysosomal dysfunction in neurodegenerative disease
Malik, B. R., Maddison, D. C., Smith, G. A., & Peters, O. M. (2019) · Molecular Brain · doi:10.1186/s13041-019-0504-x · Cited by 187
A complex of C9ORF72 and p62 uses arginine methylation to eliminate stress granules by autophagy
Chitiprolu, M., Jagow, C., Tremblay, V., Bondy‐Chorney, E., Paris, G., Savard, A., Palidwor, G., Barry, F. A., Zinman, L. H., Keith, J. L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05273-7 · Cited by 184
ULK1 and ULK2 Regulate Stress Granule Disassembly Through Phosphorylation and Activation of VCP/p97
Wang, B., Maxwell, B. A., Joo, J. H., Gwon, Y., Messing, J., Mishra, A., Shaw, T. I., Ward, A. L., Quan, H., Sakurada, S. M., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.03.027 · Cited by 185
C9ORF72: What It Is, What It Does, and Why It Matters
Smeyers, J., Banchi, E.-G., & Latouche, M. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.661447 · Cited by 198
RNA toxicity in non‐coding repeat expansion disorders
Swinnen, B., Robberecht, W., & Bosch, L. V. D. (2019) · The EMBO Journal · doi:10.15252/embj.2018101112 · Cited by 161
Umoh, M. E., Dammer, E. B., Dai, J., Duong, D. M., Lah, J. J., Levey, A. I., Gearing, M., Glass, J. D., & Seyfried, N. T. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201708202 · Cited by 159
Disrupted neuronal trafficking in amyotrophic lateral sclerosis
Burk, K., & Pasterkamp, R. J. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-01964-7 · Cited by 162
Prion-Like Propagation of Protein Misfolding and Aggregation in Amyotrophic Lateral Sclerosis
McAlary, L., Plotkin, S. S., Yerbury, J. J., & Cashman, N. R. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00262 · Cited by 160
Boivin, M., Pfister, V., Gaucherot, A., Ruffenach, F., Negroni, L., Sellier, C., & Charlet‐Berguerand, N. (2020) · The EMBO Journal · doi:10.15252/embj.2018100574 · Cited by 137
Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand
Ramesh, N., & Pandey, U. B. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00263 · Cited by 161
Molecular and Cellular Mechanisms Affected in ALS
Gall, L. L., Anakor, E., Connolly, O., Vijayakumar, U. G., Duddy, W. J., & Duguez, S. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10030101 · Cited by 152
Hautbergue, G. M., Castelli, L. M., Ferraiuolo, L., Sánchez-Martínez, Á., Cooper‐Knock, J., Higginbottom, A., Lin, Y.-H., Bauer, C. S., Dodd, J. E., Myszczynska, M. A., et al. (2017) · Nature Communications · doi:10.1038/ncomms16063 · Cited by 140
Self-citationWallings, R. L., Humble, S. W., Ward, M. E., & Wade-Martins, R. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.10.002 · Cited by 153
Macroautophagy in CNS health and disease
Griffey, C. J., & Yamamoto, A. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00588-3 · Cited by 147
Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic Opportunities
Sbodio, J. I., Snyder, S. H., & Paul, B. D. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7321 · Cited by 149
Long Non-Coding RNA (lncRNA) Roles in Cell Biology, Neurodevelopment and Neurological Disorders
Aliperti, V., Skonieczna, J., & Cerase, A. (2021) · Non-Coding RNA · doi:10.3390/ncrna7020036 · Cited by 137
Ratti, A., Gumina, V., Lenzi, P., Bossolasco, P., Fulceri, F., Volpe, C., Bardelli, D., Pregnolato, F., Maraschi, A., Fornai, F., et al. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105051 · Cited by 128
Autophagy in health and disease: From molecular mechanisms to therapeutic target
Lu, G. X., Wang, Y., Shi, Y. P., Zhang, Z., Huang, C., He, W., Wang, C., & Shen, H. (2022) · MedComm · doi:10.1002/mco2.150 · Cited by 135
Structural basis for VPS34 kinase activation by Rab1 and Rab5 on membranes
Tremel, S., Ohashi, Y., Morado, D. R., Bertram, J., Perišić, O., Brandt, L. T. L., von Wrisberg, M., Chen, Z. A., Maslen, S., Kovtun, O., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21695-2 · Cited by 131
The role of amyloid oligomers in neurodegenerative pathologies
Wells, C., Brennan, S. E., Keon, M., & Ooi, L. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.03.113 · Cited by 131
Autophagy in Age-Associated Neurodegeneration
Metaxakis, A., Ploumi, C., & Tavernarakis, N. (2018) · Cells · doi:10.3390/cells7050037 · Cited by 127
Beckers, J., Tharkeshwar, A. K., & Damme, P. V. (2021) · Autophagy · doi:10.1080/15548627.2021.1872189 · Cited by 132
Ihenacho, U. K., Nolden, K. A., Harwig, M. C., Widlansky, M. E., & Hill, R. B. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.660095 · Cited by 117
Autophagy as a common pathway in amyotrophic lateral sclerosis
Nguyen, D. K. H., Thombre, R., & Wang, J. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.04.006 · Cited by 118
Membrane Trafficking in Autophagy
Søreng, K., Neufeld, T. P., & Simonsen, A. (2017) · International review of cytology · doi:10.1016/bs.ircmb.2017.07.001 · Cited by 116
Frick, P., Sellier, C., Mackenzie, I. R., Cheng, C.-Y., Tahraoui‐Bories, J., Martinat, C., Pasterkamp, R. J., Prudlo, J., Edbauer, D., Oulad‐Abdelghani, M., et al. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0579-0 · Cited by 118
Möller, A., Bauer, C. S., Cohen, R. N., Webster, C. P., & Vos, K. J. D. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx348 · Cited by 109
Self-citationAntisense drugs make sense for neurological diseases
Bennett, C. F., Kordasiewicz, H. B., & Cleveland, D. W. (2021) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010919-023738 · Cited by 108
Astrocyte adenosine deaminase loss increases motor neuron toxicity in amyotrophic lateral sclerosis
Allen, S. P., Hall, B., Castelli, L. M., Francis, L. I., Woof, R., Siskos, A., Kouloura, E., Gray, E., Thompson, A. G., Talbot, K., et al. (2019) · Brain · doi:10.1093/brain/awy353 · Cited by 102
Self-citationThe Multiple Roles of Autophagy in Neural Function and Diseases
Li, Y., Qin, Z., & Sheng, R. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-023-01120-y · Cited by 109
Negative regulation of autophagy by UBA6-BIRC6–mediated ubiquitination of LC3
Jia, R., & Bonifacino, J. S. (2019) · eLife · doi:10.7554/elife.50034 · Cited by 99
Motor dysfunction and neurodegeneration in a C9orf72 mouse line expressing poly-PR
Hao, Z., Liu, L., Tao, Z., Wang, R., Ren, H., Sun, H., Lin, Z., Zhang, Z., Mu, C., Zhou, J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10956-w · Cited by 104
Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?
Webster, C. P., Smith, E. F., Shaw, P. J., & Vos, K. J. D. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00123 · Cited by 109
Self-citationZou, L., Liao, M., Zhen, Y., Zhu, S., Chen, X., Zhang, J. C., Hao, Y., & Liu, B. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.06.004 · Cited by 101
Endocytosis regulates TDP-43 toxicity and turnover
Liu, G., Coyne, A. N., Pei, F., Vaughan, S., Chaung, M., Zarnescu, D. C., & Buchan, J. R. (2017) · Nature Communications · doi:10.1038/s41467-017-02017-x · Cited by 97
Gene Therapy for ALS—A Perspective
Cappella, M., Ciotti, C., Cohen-Tannoudji, M., & Biferi, M. G. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184388 · Cited by 103
Rab GTPases: Switching to Human Diseases
Guadagno, N. A., & Progida, C. (2019) · Cells · doi:10.3390/cells8080909 · Cited by 97
Autophagy and Its Impact on Neurodegenerative Diseases: New Roles for TDP-43 and C9orf72
Budini, M., Buratti, E., Morselli, E., & Criollo, A. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00170 · Cited by 102
Cellular and physiological functions of C9ORF72 and implications for ALS/FTD
Pang, W., & Hu, F. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15255 · Cited by 95
Lee, Y., Baskaran, P., Gómez-Deza, J., Chen, H.-J., Nishimura, A. L., Smith, B. N., Troakes, C., Adachi, Y., Stepto, A., Petrucelli, L., et al. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx350 · Cited by 90
A C9orf72 ALS/FTD Ortholog Acts in Endolysosomal Degradation and Lysosomal Homeostasis
Corrionero, A., & Horvitz, H. R. (2018) · Current Biology · doi:10.1016/j.cub.2018.03.063 · Cited by 91
A C9orf72–CARM1 axis regulates lipid metabolism under glucose starvation-induced nutrient stressPreprint
Liu, Y., Wang, T., Ji, Y. J., Johnson, K., Liu, H., Johnson, K., Bailey, S., Suk, Y., Lu, Y., Liu, M., et al. (2018) · Genes & Development · doi:10.1101/gad.315564.118 · Cited by 84
CYLD is a causative gene for frontotemporal dementia – amyotrophic lateral sclerosis
Dobson‐Stone, C., Hallupp, M., Shahheydari, H., Ragagnin, A., Chatterton, Z., Carew‐Jones, F., Shepherd, C. E., Stefen, H., Parić, E., Fath, T., et al. (2020) · Brain · doi:10.1093/brain/awaa039 · Cited by 86
Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration
Peng, W., Minakaki, G., Nguyen, M., & Krainc, D. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00742-3 · Cited by 79
Structure of the C9orf72 ARF GAP complex that is haploinsufficient in ALS and FTD
Su, M.-Y., Fromm, S. A., Zoncu, R., & Hurley, J. H. (2020) · Nature · doi:10.1038/s41586-020-2633-x · Cited by 83
Maurel, C., Dangoumau, A., Marouillat, S., Brulard, C., Chami, A. A., Hergesheimer, R. C., Corcia, P., Blasco, H., Andres, C. R., & Vourc’h, P. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0856-0 · Cited by 82
TFEB/Mitf links impaired nuclear import to autophagolysosomal dysfunction in C9-ALS
Cunningham, K. M., Maulding, K., Ruan, K., Şentürk, M., Grima, J. C., Sung, H., Zuo, Z., Song, H., Gao, J., Dubey, S. K., et al. (2020) · eLife · doi:10.7554/elife.59419 · Cited by 80
Jung, J., Nayak, A., Schaeffer, V., Starzetz, T., Kirsch, A. K., Müller, S. P., Đikić, I., Mittelbronn, M. G. A., & Behrends, C. (2017) · eLife · doi:10.7554/elife.23063 · Cited by 79
Autophagy in Astrocytes and its Implications in Neurodegeneration
Sung, K., & Jiménez-Sánchez, M. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.041 · Cited by 78
The ALS-FTD-linked gene product, C9orf72, regulates neuronal morphogenesis via autophagy
Ho, W. Y., Tai, Y. K., Chang, J., Liang, J., Tyan, S.-H., Chen, S., Guan, J., Zhou, H., Shen, H., Koo, E. H., et al. (2019) · Autophagy · doi:10.1080/15548627.2019.1569441 · Cited by 73
Regulation of ATG and Autophagy Initiation
Li, W., & Zhang, L. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-0602-4_2 · Cited by 72
Regulation of neuronal autophagy and the implications in neurodegenerative diseases
Cai, Q., & Ganesan, D. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105582 · Cited by 70
Molecular Mechanisms of Neurodegeneration Related to C9orf72 Hexanucleotide Repeat Expansion
Leko, M. B., Župunski, V., Kirincich, J., Smilović, D., Hortobágyi, T., Hof, P. R., & Šimić, G. (2019) · Behavioural Neurology · doi:10.1155/2019/2909168 · Cited by 73
Genetics and Sex in the Pathogenesis of Amyotrophic Lateral Sclerosis (ALS): Is There a Link?
Trojsi, F., D’Alvano, G., Bonavita, S., & Tedeschi, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103647 · Cited by 75
Zhang, Y., Burberry, A., Wang, J., Sandoe, J., Ghosh, S. D., Udeshi, N. D., Svinkina, T., Mordes, D. A., Mok, J., Charlton, M. E., et al. (2018) · Genes & Development · doi:10.1101/gad.313932.118 · Cited by 73
Shaw, M. P., Higginbottom, A., McGown, A., Castelli, L. M., James, E. G., Hautbergue, G. M., Shaw, P. J., & Ramesh, T. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0629-7 · Cited by 72
Self-citationFeng, Z., Jiang, A., Mao, A., Feng, Y., Wang, W., Li, J., Zhang, X., Xing, K., & Peng, X. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.811737 · Cited by 70
C9orf72 loss-of-function: a trivial, stand-alone or additive mechanism in C9 ALS/FTD?
Braems, E., Swinnen, B., & Bosch, L. V. D. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02214-x · Cited by 72
C9ORF72 is a GDP/GTP exchange factor for Rab8 and Rab39 and regulates autophagy
Corbier, C., & Sellier, C. (2016) · Small GTPases · doi:10.1080/21541248.2016.1212688 · Cited by 73
Consequences of Rab GTPase dysfunction in genetic or acquired human diseases
Banworth, M. J., & Li, G. (2017) · Small GTPases · doi:10.1080/21541248.2017.1397833 · Cited by 68
PQLC2 recruits the C9orf72 complex to lysosomes in response to cationic amino acid starvation
Amick, J., Tharkeshwar, A. K., Talaia, G., & Ferguson, S. M. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201906076 · Cited by 68
Swerdlow, N., & Wilkins, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249661 · Cited by 66
Retromer stabilization results in neuroprotection in a model of Amyotrophic Lateral Sclerosis
Muzio, L., Sirtori, R., Gornati, D., Eleuteri, S., Fossaghi, A., Brancaccio, D., Manzoni, L., Ottoboni, L., Feo, L. D., Quattrini, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17524-7 · Cited by 65
Calió, M. L., Henriques, E., Siena, A., Bertoncini, C. R. A., Gil-Mohapel, J., & Rosenstock, T. R. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00679 · Cited by 64
Unraveling the Role of RNA Mediated Toxicity of C9orf72 Repeats in C9-FTD/ALS
Kumar, V., Hasan, G. M., & Hassan, M. I. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00711 · Cited by 67
Metadata
- Authors
- Webster, C. P., Smith, E. F., Bauer, C. S., Moller, A., Hautbergue, G. M., Ferraiuolo, L., Myszczynska, M. A., Higginbottom, A., Walsh, M. J., Whitworth, A. J., Kaspar, B. K., Meyer, K., Shaw, P. J., Grierson, A. J., & De Vos, K. J.
- Affiliations
- University of Sheffield (GB)
- Nationwide Children's Hospital (US)
- ORCID
- Venue
- The EMBO Journal
- Published
- 2016-06-22
- Volume
- 35
- Issue
- 15
- Pages
- 1656-1676
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC4969571
- OpenAlex
- W2467513012
- Cited by
- 404
- References
- 75
- Citations by year
- 2026: 24 · 2025: 25 · 2024: 35 · 2023: 36 · 2022: 29 · 2021: 50 · 2020: 55 · 2019: 47 · 2018: 46 · 2017: 43 · 2016: 13
- FWCI
- 37.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The EMBO Journal (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Funders
- Thierry Latran Foundation (RoCIP)
- Medical Research Council (MR/K005146/1, MR/M013251/1)
- Alzheimer's Society (260 (AS‐PG‐15‐023))
- University of Sheffield (Moody Family Endowment)
- European Union Seventh Framework Programme (EuroMOTOR 259867, 303101)
- Motor Neurone Disease Association (DeVos/Oct13/870‐892)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- C9orf72, Rab1A, ULK1 complex, autophagy initiation, amyotrophic lateral sclerosis, frontotemporal dementia, haploinsufficiency, phagophore, induced neurons, protein isoforms
- MeSH terms
- Autophagy-Related Protein-1 Homolog, C9orf72 Protein, Autophagy, Cell Physiological Phenomena, Cells, Cultured, Humans, Neurons, Proteins, rab1 GTP-Binding Proteins, Intracellular Signaling Peptides and Proteins, Frontotemporal Dementia
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
