The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking
Open accessAbstract
Intronic expansion of a hexanucleotide GGGGCC repeat in the chromosome 9 open reading frame 72 (C9ORF72) gene is the major cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. However, the cellular function of the C9ORF72 protein remains unknown. Here, we demonstrate that C9ORF72 regulates endosomal trafficking. C9ORF72 colocalized with Rab proteins implicated in autophagy and endocytic transport: Rab1, Rab5, Rab7 and Rab11 in neuronal cell lines, primary cortical neurons and human spinal cord motor neurons, consistent with previous predictions that C9ORF72 bears Rab guanine exchange factor activity. Consistent with this notion, C9ORF72 was present in the extracellular space and as cytoplasmic vesicles. Depletion of C9ORF72 using siRNA inhibited transport of Shiga toxin from the plasma membrane to Golgi apparatus, internalization of TrkB receptor and altered the ratio of autophagosome marker light chain 3 (LC3) II:LC3I, indicating that C9ORF72 regulates endocytosis and autophagy. C9ORF72 also colocalized with ubiquilin-2 and LC3-positive vesicles, and co-migrated with lysosome-stained vesicles in neuronal cell lines, providing further evidence that C9ORF72 regulates autophagy. Investigation of proteins interacting with C9ORF72 using mass spectrometry identified other proteins implicated in ALS; ubiquilin-2 and heterogeneous nuclear ribonucleoproteins, hnRNPA2/B1 and hnRNPA1, and actin. Treatment of cells overexpressing C9ORF72 with proteasome inhibitors induced the formation of stress granules positive for hnRNPA1 and hnRNPA2/B1. Immunohistochemistry of C9ORF72 ALS patient motor neurons revealed increased colocalization between C9ORF72 and Rab7 and Rab11 compared with controls, suggesting possible dysregulation of trafficking in patients bearing the C9ORF72 repeat expansion. Hence, this study identifies a role for C9ORF72 in Rab-mediated cellular 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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Interestingly, the impaired endocytic signaling has been observed during C9ORF72 mutated conditions in C9ORF72 ALS/FTD patients as well as the SH-SY5Y cell line model, suggesting that the expression of C9ORF72 modulates endocytosis [172,173].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [172]
Experimental — accuracy not yet measuredIn the citing paper
“The C9orf72 protein belongs to the DENN (differentially expressed in normal and neoplastic cells) family [143,144] and binds the GTPases RAB7 and RAB11, which are involved in endosome maturation and recycling [145].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [145]
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
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
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
Measurement of co‐localization of objects in dual‐colour confocal images
Manders, E. M. M., Verbeek, F. J., & Aten, J. A. (1993) · Journal of Microscopy · doi:10.1111/j.1365-2818.1993.tb03313.x · Cited by 2,132
Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS
Kim, H. J., Kim, N. C., Wang, Y., Scarborough, E. A., Moore, J., Diaz, Z., MacLea, K. S., Freibaum, B. D., Li, S., Molliex, A., et al. (2013) · Nature · doi:10.1038/nature11922 · Cited by 1,478
The C9orf72 GGGGCC Repeat Is Translated into Aggregating Dipeptide-Repeat Proteins in FTLD/ALS
Mori, K., Weng, S., Arzberger, T., May, S., Rentzsch, K., Kremmer, E., Schmid, B., Kretzschmar, H. A., Cruts, M., Broeckhoven, C. V., et al. (2013) · Science · doi:10.1126/science.1232927 · Cited by 1,248 · cited 2×
“Similarly, it remains unclear how C9ORF72 repeat expansions trigger ALS pathology, although haploinsufficiency due to impaired transcription/splicing, leading to reduced C9ORF72 protein expression (up to 50%) (8), RNA dysfunction, and unconventional translation of the repeat to generate insoluble polypeptides, are pos…”
BackgroundRegulation of Small GTPases by GEFs, GAPs, and GDIs
Cherfils, J., & Zeghouf, M. (2013) · Physiological Reviews · doi:10.1152/physrev.00003.2012 · Cited by 1,245 · cited 11×
“C9ORF72 colocalized strongly with Rabs implicated in autophagy and endosomal transport: Rab1, Rab7, Rab5 and Rab11 (Fig.”
BackgroundInfluentialMajounie, E., Renton, A. E., Mok, K., Dopper, E. G., Waite, A., Rollinson, S., Chiò, A., Restagno, G., Nicolaou, N., Simon-Sanchez, J., et al. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70043-1 · Cited by 1,210
Feature-based prediction of non-classical and leaderless protein secretion
Bendtsen, J. D., Jensen, L. J., Blom, N., von HEIJNE, G., & Brunak, S. (2004) · Protein Engineering Design and Selection · doi:10.1093/protein/gzh037 · Cited by 1,179 · cited 1×
“1F), presumably via nonclassical means because bioinformatics analysis predicted that a signal leader peptide was not present in C9ORF72 (Secretome P) (27).”
BackgroundMutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia
Deng, H.-X., Chen, W., Hong, S.-T., Boycott, K. M., Gorrie, G. H., Siddique, N., Yang, Y., Fecto, F., Shi, Y., Zhai, H., et al. (2011) · Nature · doi:10.1038/nature10353 · Cited by 1,174 · cited 2×
“Defects in protein degradation are increasingly implicated in ALS pathogenesis (19) and mutations in ubiquilin-2 (20), which regulates autophagy and the UPS by binding/transport of protein cargo (21), also cause ALS/FTD.”
BackgroundRab7: A Key to Lysosome Biogenesis
Bucci, C., Thomsen, P., Nicoziani, P., McCarthy, J., & van Deurs, B. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.2.467 · Cited by 1,111
Flagged first, then by citations
Research works printed but not linked: 1
- Arancibia-Carcamo, 2006, Chapter 6. Frontiers in Neuroscience
Cited by
Sorted by citations
Items 101–200 of 481
Proteomics Approaches for Biomarker and Drug Target Discovery in ALS and FTD
Hedl, T. J., San Gil, R., Cheng, F., Rayner, S. L., Davidson, J. M., De Luca, A., Villalva, M. D., Ecroyd, H., Walker, A. K., & Lee, A. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00548 · Cited by 87
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
“Recent studies have suggested that C9orf72 regulates membrane trafficking, the autophagy–lysosome pathway, and autoimmunity (Farg et al. 2014; Amick et al. 2016; Burberry et al. 2016; O’Rourke et al. 2016; Sellier et al. 2016; Sullivan et al. 2016; Ugolino et al. 2016; Webster et al. 2016; Yang et…”
Proteostasis impairment in ALS
Ruegsegger, C., & Saxena, S. (2016) · Brain Research · doi:10.1016/j.brainres.2016.03.032 · Cited by 88
Psychiatric Presentations of C9orf72 Mutation: What Are the Diagnostic Implications for Clinicians?
Ducharme, S., Bajestan, S., Dickerson, B. C., & Voon, V. (2017) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/appi.neuropsych.16090168 · Cited by 84
Impaired Mitophagy Plays a Role in Denervation of Neuromuscular Junctions in ALS Mice
Rogers, R. S., Tungtur, S., Tanaka, T., Nadeau, L. L., Badawi, Y., Wang, H., Ni, H.-M., Ding, W.-X., & Nishimune, H. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00473 · Cited by 83
C9orf72-FTD/ALS pathogenesis: evidence from human neuropathological studies
Vatsavayai, S. C., Nana, A. L., Yokoyama, J. S., & Seeley, W. W. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1921-0 · Cited by 82
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
Appel, J. R., Ye, S., Tang, F., Sun, D., Zhang, H., Mei, L., & Xiong, W. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.3621-17.2018 · Cited by 86
“It is important to note here the relevance of these findings, as microglial depletion of C9orf72 [a regulator of endosomal trafficking (Farg et al., 2014)] results in similar enlargement of LAMP1 vesicles, as observed in VPS35CX3CR1 microglia (O’Rourke et al., 2016), and microglial depletion of…”
ResultStructure 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
Rizzu, P., Blauwendraat, C., Heetveld, S., Lynes, E. M., Castillo-Lizardo, M., Dhingra, A., Pyż, E., Hobert, M. A., Synofzik, M., Simón‐Sánchez, J., et al. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0306-7 · Cited by 88
Impairment of Lysosome Function and Autophagy in Rare Neurodegenerative Diseases
Darios, F. D., & Stévanin, G. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.02.033 · Cited by 79
Cryo-EM structure of C9ORF72–SMCR8–WDR41 reveals the role as a GAP for Rab8a and Rab11a
Tang, D., Sheng, J., Xu, L., Zhan, X., Liu, J., Jiang, H., Shu, X., Liu, X., Zhang, T., Jiang, L., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2002110117 · Cited by 82
“The CSW complex has been reported to function as a GEF of Rab7a, Rab8a, Rab11a, Rab39a, and Rab39b (14, 17, 31).”
BackgroundModeling ALS and FTD with iPSC-derived neurons
Lee, S., & Huang, E. J. (2015) · Brain Research · doi:10.1016/j.brainres.2015.10.003 · Cited by 79
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
“Loss of function of C9orf72 also disrupts autophagy and lysosomal function in multiple cell types (Farg et al., 2014; Ji et al., 2017; O’Rourke et al., 2015; Sellier et al., 2016; Shi et al., 2018; Sullivan et al., 2016; Ugolino et al., 2016; Webster et al., 2016; Yang et al., 2016; Zhu et al., 2020), suggesting a mec…”
BackgroundŠket, P., Pohleven, J., Kovanda, A., Štalekar, M., Župunski, V., Zalar, M., Plavec, J., & Rogelj, B. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.09.012 · Cited by 76
Exploring the genetics and non-cell autonomous mechanisms underlying ALS/FTLD
Chen, H., Kankel, M. W., Su, S. C., Han, S., & Ofengeim, D. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0060-4 · Cited by 74
The Role of Rab Proteins in Neuronal Cells and in the Trafficking of Neurotrophin Receptors
Bucci, C., Alifano, P., & Cogli, L. (2014) · Membranes · doi:10.3390/membranes4040642 · Cited by 77
Haase, G., & Rabouille, C. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00448 · Cited by 78
Autophagy and Neurodegeneration: Insights from a Cultured Cell Model of ALS
Navone, F., Genevini, P., & Borgese, N. (2015) · Cells · doi:10.3390/cells4030354 · Cited by 74
Proteostatic imbalance and protein spreading in amyotrophic lateral sclerosis
Cicardi, M. E., Marrone, L., Azzouz, M., & Trotti, D. (2021) · The EMBO Journal · doi:10.15252/embj.2020106389 · Cited by 75
Todd, T. W., & Petrucelli, L. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13623 · Cited by 73
“Furthermore, siRNA-mediated knockdown of C9orf72 in neuronal cell lines resulted in a decrease in endocytic trafficking, as well as a disruption in autophagosome formation (Farg et al. 2014).”
BackgroundInfluentialImpaired protein degradation in FTLD and related disorders
Götzl, J. K., Lang, C. M., Haass, C., & Capell, A. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.008 · Cited by 75
Rab7 induces clearance of α‐synuclein aggregates
Dinter, E., Saridaki, T., Nippold, M., Plum, S., Diederichs, L., Komnig, D., Fensky, L., May, C., Marcus, K., Voigt, A., et al. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13712 · Cited by 73
Intrinsic Disorder in Proteins with Pathogenic Repeat Expansions
Darling, A. L., & Uversky, V. N. (2017) · Molecules · doi:10.3390/molecules22122027 · Cited by 75
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
Meijboom, K. E., Abdallah, A., Fordham, N. P., Nagase, H., Rodríguez, T., Kraus, C., Gendron, T. F., Krishnan, G., Esanov, R., Andrade, N. S., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33332-7 · Cited by 78
Sundaramoorthy, V., Sultana, J. M., & Atkin, J. D. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00400 · Cited by 74
Self-citationRegulation 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
“Additionally, a hexanucleotide repeat expansion in the ALS-causing C9ORF72 gene (DeJesus-Hernandez et al., 2011; Renton et al., 2011) was reported to be involved in endocytic vesicle trafficking and autophagy likely through forming a complex with Smith-Magenis syndrome chromosome region, candidate 8 (SMCR8) and WD rep…”
C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia
Mizielinska, S., & Isaacs, A. M. (2014) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000130 · Cited by 73
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
“It was shown that C9orf72 interacts with hnRNP-U, hnRNP-F, hnRNP-K [51], hnRNP-A2/B1, and hnRNP-A1 [28], while hnRNP A1 and hnRNP H colocalize with RNA foci [70, 71].”
BackgroundA Systematic Review of Suggested Molecular Strata, Biomarkers and Their Tissue Sources in ALS
Vijayakumar, U. G., Milla, V., Stafford, M. Y. C., Bjourson, A. J., Duddy, W. J., & Duguez, S. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00400 · Cited by 71
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, J., Abeliovich, H., Acevedo‐Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Kölner Universitäts PublikationsServer (Universität zu Köln) · doi:10.5167/uzh-131237 · Cited by 69
Multiple Types of Guanine Nucleotide Exchange Factors (GEFs) for Rab Small GTPases
Ishida, M., Oguchi, M. E., & Fukuda, M. (2016) · Cell Structure and Function · doi:10.1247/csf.16008 · Cited by 68
Emerging Perspectives on Dipeptide Repeat Proteins in C9ORF72 ALS/FTD
Schmitz, A., Marques, J. P., Oertig, I., Maharjan, N., & Saxena, S. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.637548 · 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
“As C9orf72 also colocalizes with several of these Rabs, it is likely to have a function in membrane trafficking [33].”
BackgroundInfluentialC9ORF72 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
Nuclear trafficking in amyotrophic lateral sclerosis and frontotemporal lobar degeneration
Mihevc, S. P., Darovic, S., Kovanda, A., Česnik, A. B., Župunski, V., & Rogelj, B. (2016) · Brain · doi:10.1093/brain/aww197 · Cited by 62
ALS: Recent Developments from Genetics Studies
Therrien, M., Dion, P. A., & Rouleau, G. A. (2016) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-016-0658-1 · Cited by 65
An amyloid-like cascade hypothesis for C9orf72 ALS/FTD
Edbauer, D., & Haass, C. (2015) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.10.009 · Cited by 69
mRNP assembly, axonal transport, and local translation in neurodegenerative diseases
Khalil, B., Morderer, D., Price, P. L., Liu, F., & Rossoll, W. (2018) · Brain Research · doi:10.1016/j.brainres.2018.02.018 · Cited by 66
Research progress on the role of extracellular vesicles in neurodegenerative diseases
Li, Z., Wang, X., Wang, X., Yi, X., Wong, Y. K., Wu, J., Xie, F., Hu, D., Wang, Q., Wang, J., et al. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00375-9 · Cited by 67
“GGG GCC repeats in C9orf72 are the most common cause of ALS and the basis of ALS vesicle trafficking [155, 156].”
BackgroundDecreased function of survival motor neuron protein impairs endocytic pathways
Dimitriadi, M., Derdowski, A., Kalloo, G., Maginnis, M. S., O’Hern, P., Bliska, B., Sorkaç, A., Nguyen, K. C. Q., Cook, S. J., Poulogiannis, G., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1600015113 · Cited by 64
Hypo- and Hyper-Assembly Diseases of RNA–Protein Complexes
Shukla, S., & Parker, R. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.05.005 · Cited by 64
Autophagy in neuroinflammatory diseases
Muller, S., Brun, S., René, F., Seze, J. D., Loeffler, J., & Jeltsch‐David, H. (2017) · Autoimmunity Reviews · doi:10.1016/j.autrev.2017.05.015 · Cited by 66
Lu, Y., Wang, X., Gu, Q., Wang, J., Sui, Y., Wu, J., & Feng, J. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01129-8 · Cited by 63
“According to the current researches, hnRNPA1 and A2/ B1 were verified to co-localize with TDP-43 in the cytoplasm of atrophic muscle fibers [143], as well as with C9ORF72 [145], DNAJB6 [146] and SMN1 [147], respectively, in stress granules.”
Steinruecke, M., Lonergan, R. M., Selvaraj, B. T., Chandran, S., Castro, B. D., & Stavrou, M. (2023) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x231153281 · Cited by 63
Current Advances and Limitations in Modeling ALS/FTD in a Dish Using Induced Pluripotent Stem Cells
Guo, W., Fumagalli, L., Prior, R. C., & Bosch, L. V. D. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00671 · Cited by 65
“Consistent with the prediction of its function, C9ORF72 protein was found to colocalize with Rab proteins and to be involved in endosomal trafficking and autophagy (Farg et al., 2014).”
BackgroundCali, C. P., Patiño, M., Tai, Y. K., Ho, W. Y., McLean, C., Morris, C. M., Seeley, W. W., Miller, B. L., Gaig, C., Vonsattel, J. P., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02045-5 · Cited by 64
STING signaling in the brain: Molecular threats, signaling activities, and therapeutic challenges
Yang, K., Tang, Z., Xing, C., & Yan, N. (2023) · Neuron · doi:10.1016/j.neuron.2023.10.014 · Cited by 63
The Enigmatic Role of C9ORF72 in Autophagy
Nassif, M., Woehlbier, U., & Manque, P. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00442 · Cited by 68
Insights of Endocytosis Signaling in Health and Disease
Pathak, C., Vaidya, F. U., Waghela, B. N., Jaiswara, P. K., Gupta, V. K., Kumar, A., Rajendran, B. K., & Ranjan, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032971 · Cited by 59
Role of Extracellular Vesicles in Amyotrophic Lateral Sclerosis
Ferrara, D., Pasetto, L., Bonetto, V., & Basso, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00574 · Cited by 65
Lorente Pons, A., Higginbottom, A., Cooper‐Knock, J., Alrafiah, A., Alofi, E., Kirby, J., Shaw, P. J., Wood, J. D., & Highley, J. R. (2020) · The Journal of Pathology · doi:10.1002/path.5455 · Cited by 57
Wang, H., Kodavati, M. M., Britz, G. W., & Hegde, M. L. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.784361 · Cited by 59
Protein Quality Control and the Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Continuum
Shahheydari, H., Ragagnin, A., Walker, A. K., Toth, R. P., Vidal, M., Jagaraj, C. J., Perri, E. R., Konopka, A., Sultana, J. M., & Atkin, J. D. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00119 · Cited by 61
Self-citationStress Granules and Neurodegenerative Disorders: A Scoping Review
Asadi, M. R., Moslehian, M. S., Sabaie, H., Jalaiei, A., Ghafouri‐Fard, S., Taheri, M. N., & Rezazadeh, M. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.650740 · Cited by 60
ALS and FTD: Where RNA metabolism meets protein quality control
Mandrioli, J., Mediani, L., Alberti, S., & Carra, S. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.06.003 · Cited by 63
Implications of Selective Autophagy Dysfunction for ALS Pathology
Vicencio, E., Beltrán, S., Labrador, L., Manque, P., Nassif, M., & Woehlbier, U. (2020) · Cells · doi:10.3390/cells9020381 · Cited by 60
“Moreover, C9ORF72 interacts with RAB1, RAB5, RAB7, and RAB11 (all proteins involved in autophagy) [77,173,174].”
BackgroundGenetic models of C9orf72: what is toxic?
Moens, T. G., Partridge, L., & Isaacs, A. M. (2017) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2017.01.006 · Cited by 57
Iyer, S., Subramanian, V., & Acharya, K. R. (2018) · PeerJ · doi:10.7717/peerj.5815 · Cited by 57
“In the present case, far-western analysis was used as a rapid qualitative method to probe the previously hypothesized interaction between C9orf72 and Rab proteins (Farg et al., 2014).”
BackgroundMethodIN VITRO AND IN VIVO MODELS OF AMYOTROPHIC LATERAL SCLEROSIS: AN UPDATED OVERVIEW
de Gois, A. M., de Mendonça, D. M. F., Freire, M. A. M., & dos Santos, J. R. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.03.012 · Cited by 63
Guo, W., Vandoorne, T., Steyaert, J., Staats, K. A., & Bosch, L. V. D. (2020) · Brain · doi:10.1093/brain/awaa022 · Cited by 58
“C9ORF72 co-localized with Rab proteins, which are implicated in autophagy and endocytic transport in human spinal motor neurons, indicating a role in Rab-mediated endosomal trafficking in ALS (Farg et al., 2014).”
BackgroundC9orf72: At the intersection of lysosome cell biology and neurodegenerative disease
Amick, J., & Ferguson, S. M. (2017) · Traffic · doi:10.1111/tra.12477 · Cited by 58
Therrien, M., & Parker, J. A. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00085 · Cited by 64
“Recently, C9ORF72 was shown to be implicated in endosomal trafficking (Farg et al., 2014), confirming its role as a DENN protein.”
BackgroundJaiswal, M. K. (2014) · Molecular and Cellular Therapies · doi:10.1186/2052-8426-2-26 · Cited by 56
Structural Variants May Be a Source of Missing Heritability in sALS
Theunissen, F., Flynn, L. L., Anderton, R. S., Mastaglia, F. L., Pytte, J., Jiang, L., Hodgetts, S. I., Burns, D. K., Saunders, A. M., Fletcher, S., et al. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00047 · Cited by 56
Network Analyses Reveal Novel Aspects of ALS Pathogenesis
Sanhueza, M., Chai, A., Smith, C., McCray, B. A., Simpson, T. I., Taylor, J. P., & Pennetta, G. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005107 · Cited by 53
“These data were confirmed by a recent report showing aberrant accumulation of RAB7- and RAB11-positive vesicles in post-mortem tissues of ALS patients [53].”
BackgroundResultThe Spectrum of C9orf72-mediated Neurodegeneration and Amyotrophic Lateral Sclerosis
Cooper‐Knock, J., Kirby, J., Highley, J. R., & Shaw, P. J. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0342-1 · Cited by 58
Dickson, D. W., Baker, M., Jackson, J. L., DeJesus‐Hernandez, M., Finch, N. A., Tian, S., Heckman, M. G., Pottier, C. P., Gendron, T. F., Murray, M. E., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0797-0 · Cited by 54
Liu, Y., Andreucci, A., Iwamoto, N., Yin, Y., Yang, H., Liu, F., Bulychev, A., Hu, X. S., Lin, X., Lamore, S. D., et al. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.04.007 · Cited by 56
The Genetics of Monogenic Frontotemporal Dementia
Takada, L. T. (2015) · Dementia & Neuropsychologia · doi:10.1590/1980-57642015dn93000003 · Cited by 56
Old versus New Mechanisms in the Pathogenesis of ALS
Rossi, S., Cozzolino, M., & Carrı̀, M. T. (2016) · Brain Pathology · doi:10.1111/bpa.12355 · Cited by 55
Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases
Quinn, C. C., & Elman, L. B. (2020) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000000911 · Cited by 60
McAlpine, W., Sun, L., Wang, K.-W., Liu, A., Jain, R., Miguel, M. S., Wang, J., Zhang, Z., Hayse, B., McAlpine, S. G., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814753115 · Cited by 57
“A role for the SWC complex in autophagy (2–6) and endocytic transport (7) has been established by studies documenting defects in these processes in the absence of a single complex component.”
BackgroundWang, M., Wang, H., Tao, Z., Qin, X., Hao, Z., Prehn, J. H. M., Zhen, X., Wang, G., & Ying, Z. (2020) · Aging Cell · doi:10.1111/acel.13126 · Cited by 52
“…role in the regulation of endosomal trafficking and autophagy at multiple steps (Amick, Roczniak-Ferguson, & Ferguson, 2016; Corrionero & Horvitz, 2018; Farg et al., 2014; Sellier et al., 2016; Shi et al., 2018; Sullivan et al., 2016; Ugolino et al., 2016; Webster et al., 2016; Yang et al., 2016).”
Marian, O. C., Teo, J. D., Lee, J. Y., Song, H., Kwok, J. B., Landin-Romero, R., Halliday, G., & Don, A. S. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01544-7 · Cited by 50
“Physiologically, C9orf72 is required for endosomal trafficking, autophagy and lysosomal biogenesis [23, 24].”
BackgroundVatovec, S., Kovanda, A., & Rogelj, B. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.04.015 · Cited by 53
Edens, B. M., Miller, N., & Ma, Y. C. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00044 · Cited by 52
New insights into the gene expression associated to amyotrophic lateral sclerosis
Recabarren-Leiva, D., & Alarcón, M. A. (2017) · Life Sciences · doi:10.1016/j.lfs.2017.12.016 · Cited by 49
Role of Autophagy Pathway in Parkinson’s Disease and Related Genetic Neurological Disorders
Themistokleous, C., Bagnoli, E., Parulekar, R., & Muqit, M. M. K. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168144 · Cited by 51
Zhou, X., Sun, L., Brady, O. A., Murphy, K. A., & Hu, F. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0412-1 · Cited by 49
Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?
Mazzon, E., & Giacoppo, S. (2016) · Neural Regeneration Research · doi:10.4103/1673-5374.197125 · Cited by 48
Marine Arthropods as a Source of Antimicrobial Peptides
Saucedo-Vázquez, J. P., Gushque, F., Vispo, N. S., Rodríguez, J. A., Gomezjurado, M. E. G., Alberício, F., Tellkamp, M. P., & Alexis, F. (2022) · Marine Drugs · doi:10.3390/md20080501 · Cited by 48
Linking RNA Dysfunction and Neurodegeneration in Amyotrophic Lateral Sclerosis
Barmada, S. J. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0340-3 · Cited by 52
Stress Granules and ALS: A Case of Causation or Correlation?
Fernandes, N., Eshleman, N., & Buchan, J. R. (2018) · Advances in neurobiology · doi:10.1007/978-3-319-89689-2_7 · Cited by 46
The endolysosomal pathway and ALS/FTD
Todd, T. W., Shao, W., Zhang, Y., & Petrucelli, L. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.09.004 · Cited by 45
Prion-like mechanisms in amyotrophic lateral sclerosis
Ayers, J. I., & Cashman, N. R. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63945-5.00018-0 · Cited by 44
C9orf72 isoforms in Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration
Xiao, S., MacNair, L., McLean, J. R., McGoldrick, P., McKeever, P. M., Soleimani, S., Keith, J. L., Zinman, L. H., Rogaeva, E. A., & Robertson, J. (2016) · Brain Research · doi:10.1016/j.brainres.2016.04.062 · Cited by 48
Overview of Crosstalk Between Multiple Factor of Transcytosis in Blood Brain Barrier
Tjakra, M., Wang, Y., Vania, V., Hou, Z., Durkan, C., Wang, N., & Wang, G. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01436 · Cited by 45
“• Endosomal rearrangement (Rabs) instability (Farg et al., 2014)”
Autophagy in motor neuron disease: Key pathogenetic mechanisms and therapeutic targets
Mis, M. S. C., Brajkovic, S., Frattini, E., Fonzo, A. D., & Corti, S. P. (2016) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2016.01.012 · Cited by 47
“However, the up-regulation of LC3-II, mediated by siRNA knockdown of C9ORF72, did not support the role of autophagy defect as the key pathogenic event in C9ORF72-associated pathology (Farg et al., 2014).”
Wen, X., Westergard, T., Pasinelli, P., & Trotti, D. (2016) · Neuroscience Letters · doi:10.1016/j.neulet.2016.09.007 · Cited by 45
Taskesen, E., Mishra, A., van der Sluis, S., Ferrari, R., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B., Dobson‐Stone, C., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-09320-z · Cited by 41
C9orf72 is essential for neurodevelopment and motility mediated by Cyclin G1
Yeh, T., Liu, H.-F., Li, Y.-W., Lu, C.-S., Shih, H., Chiu, C., Lin, S., Huang, Y.-C., & Cheng, Y. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.03.002 · Cited by 51
Clayton, E. L., Milioto, C., Muralidharan, B., Norona, F. E., Edgar, J. R., Soriano, A., Jafar‐Nejad, P., Rigo, F., Collinge, J., & Isaacs, A. M. (2018) · Brain · doi:10.1093/brain/awy284 · Cited by 45
The Genetics of C9orf72 ExpansionsPreprint
Gijselinck, I., Cruts, M., & Broeckhoven, C. V. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026757 · Cited by 43
Ruffoli, R., Bartalucci, A., Frati, A., & Fornai, F. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00341 · Cited by 42
“Very recently C9orf72 was described to be involved in the trafficking of autophagy vesicles (Farg et al., 2014).”
Satoh, J., Yamamoto, Y., Kitano, S., Takitani, M., Asahina, N., & Kino, Y. (2014) · Journal of Central Nervous System Disease · doi:10.4137/jcnsd.s18103 · Cited by 44
P38α MAPK Signaling—A Robust Therapeutic Target for Rab5-Mediated Neurodegenerative Disease
Germann, U. A., & Alam, J. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155485 · Cited by 40
Payne, N. L., Sylvain, A., O’Brien, C., Herszfeld, D., Sun, G., & Bernard, C. C. A. (2014) · New Biotechnology · doi:10.1016/j.nbt.2014.05.001 · Cited by 41
“The GGGCC repeat expansion in C9ORF72, which has recently been shown to play a role in endosomal trafficking [99], is the most common pathogenic mutation in ALS and results in the formation”
Background
Metadata
- Authors
- Farg, M. A., Sundaramoorthy, V., Sultana, J. M., Yang, S., Atkinson, R. A. K., Levina, V., Halloran, M. A., Gleeson, P. A., Blair, I. P., Soo, K. Y., King, A. E., & Atkin, J. D.
- Affiliations
- Macquarie University (AU)
- University of Tasmania (AU)
- La Trobe University (AU)
- The University of Melbourne (AU)
- Corresponding author
- Atkin, Julie D.
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-02-18
- Volume
- 23
- Issue
- 13
- Pages
- 3579-3595
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC5886132
- OpenAlex
- W2102327538
- Cited by
- 478
- References
- 66
- Citations by year
- 2026: 8 · 2025: 22 · 2024: 25 · 2023: 35 · 2022: 24 · 2021: 58 · 2020: 52 · 2019: 39 · 2018: 39 · 2017: 50 · 2016: 57 · 2015: 50 · 2014: 19
- FWCI
- 38.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Human Molecular Genetics (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc)
- eCite Digital Repository (University of Tasmania) (submittedVersion, cc-by-nc)
- Own your potential (DEAKIN) (submittedVersion)
- Figshare (submittedVersion, cc-by-nc)
- Funders
- Motor Neurone Disease Research Institute of Australia
- La Trobe University
- University of Wollongong
- Medical Research Council
- National Health and Medical Research Council (1004670, 1030513, 1006141)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- C9orf72, amyotrophic lateral sclerosis, frontotemporal dementia, hexanucleotide repeat expansion, endosomal trafficking, Rab GTPases, autophagy, endocytosis, UBQLN2, hnRNP A1, HNRNPA2B1, stress granules, motor neurons, lysosomes, LC3, proteasome
- MeSH terms
- Autophagy-Related Proteins, C9orf72 Protein, rab7 GTP-Binding Proteins, rab11 GTP-Binding Proteins, Amyotrophic Lateral Sclerosis, Animals, Biological Transport, Humans, Proteins, Endosomes, Mass Spectrometry, rab GTP-Binding Proteins, Adaptor Proteins, Vesicular Transport, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Adaptor Proteins, Signal Transducing, Mice, 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
