HSP110 is a modulator of amyloid beta (Aβ) aggregation and proteotoxicity.
Abeta
C. elegans
aggregation
chaperones
proteostasis
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
23 Aug 2024
23 Aug 2024
Historique:
revised:
01
07
2024
received:
25
01
2024
accepted:
13
08
2024
medline:
24
8
2024
pubmed:
24
8
2024
entrez:
24
8
2024
Statut:
aheadofprint
Résumé
Chaperones safeguard protein homeostasis by promoting folding and preventing aggregation. HSP110 is a cytosolic chaperone that functions as a nucleotide exchange factor for the HSP70 cycle. Together with HSP70 and a J-domain protein (JDP), HSP110 maintains protein folding and resolubilizes aggregates. Interestingly, HSP110 is vital for the HSP70/110/JDP-mediated disaggregation of amyloidogenic proteins implicated in neurodegenerative diseases (i.e., α-synuclein, HTT, and tau). However, despite its abundance, HSP110 remains still an enigmatic chaperone, and its functional spectrum is not very well understood. Of note, the disaggregation activity of neurodegenerative disease-associated amyloid fibrils showed both beneficial and detrimental outcomes in vivo. To gain a more comprehensive understanding of the chaperone HSP110 in vivo, we analyzed its role in neuronal proteostasis and neurodegeneration in C. elegans. Specifically, we investigated the role of HSP110 in the regulation of amyloid beta peptide (Aβ) aggregation using an established Aβ-C. elegans model that mimics Alzheimer's disease pathology. We generated a novel C. elegans model that over-expresses hsp-110 pan-neuronally, and we also depleted hsp-110 by RNAi-mediated knockdown. We assessed Aβ aggregation in vivo and in situ by fluorescence lifetime imaging. We found that hsp-110 over-expression exacerbated Aβ aggregation and appeared to reduce the conformational variability of the Aβ aggregates, whereas hsp-110 depletion reduced aggregation more significantly in the IL2 neurons, which marked the onset of Aβ aggregation. HSP-110 also plays a central role in growth and fertility as its over-expression compromises nematode physiology. In addition, we found that HSP-110 modulation affects the autophagy pathway. While hsp-110 over-expression impairs the autophagic flux, a depletion enhances it. Thus, HSP-110 regulates multiple nodes of the proteostasis network to control amyloid protein aggregation, disaggregation, and autophagic clearance.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : KI1988/3-2
Organisme : Deutsche Forschungsgemeinschaft
ID : KI1988/7-1
Informations de copyright
© 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.
Références
Ayala Mariscal, S. M., Pigazzini, M. L., Richter, Y., Özel, M., Grothaus, I. L., Protze, J., Ziege, K., Kulke, M., ElBediwi, M., Vermaas, J. V., Colombi Ciacchi, L., Köppen, S., Liu, F., & Kirstein, J. (2022). Identification of a HTT‐specific binding motif in DNAJB1 essential for suppression and disaggregation of HTT. Nature Communications, 13, 4692.
Balchin, D., Hayer‐Hartl, M., & Hartl, F. U. (2016). In vivo aspects of protein folding and quality control. Science, 353, aac4354.
Berger, S. E., Nolte, A. M., Kamiya, E., & Hines, J. K. (2020). Three J‐proteins impact Hsp104‐mediated variant‐specific prion elimination: A new critical role for a low‐complexity domain. Current Genetics, 66, 51–58.
Brehme, M., Voisine, C., Rolland, T., Wachi, S., Soper, J. H., Zhu, Y., Orton, K., Villella, A., Garza, D., Vidal, M., Ge, H., & Morimoto, R. I. (2014). A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease. Cell Reports, 9, 1135–1150.
Chang, J. T., Kumsta, C., Hellman, A. B., Adams, L. M., & Hansen, M. (2017). Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging. eLife, 6, e18459. https://doi.org/10.7554/eLife.18459
Dobriyal, N., Tripathi, P., Sarkar, S., Tak, Y., Verma, A. K., & Sahi, C. (2017). Partial dispensability of Djp1's J domain in peroxisomal protein import in Saccharomyces cerevisiae results from genetic redundancy with another class II J protein, Caj1. Cell Stress & Chaperones, 22, 445–452.
Eroglu, B., Moskophidis, D., & Mivechi, N. F. (2010). Loss of Hsp110 leads to age‐dependent tau hyperphosphorylation and early accumulation of insoluble amyloid beta. Molecular and Cellular Biology, 30, 4626–4643.
Fares, H., & Grant, B. (2002). Deciphering endocytosis in Caenorhabditis elegans. Traffic, 3, 11–19.
Feleciano, D. R., Juenemann, K., Iburg, M., Brás, I. C., Holmberg, C. I., & Kirstein, J. (2019). Crosstalk between chaperone‐mediated protein disaggregation and proteolytic pathways in aging and disease. Frontiers in Aging Neuroscience, 11, 9.
Gallrein, C., Iburg, M., Michelberger, T., Koçak, A., Puchkov, D., Liu, F., Ayala Mariscal, S. M., Nayak, T., Kaminski Schierle, G. S., & Kirstein, J. (2021). Novel amyloid‐beta pathology C. Elegans model reveals distinct neurons as seeds of pathogenicity. Progress in Neurobiology, 198, 101907.
Gao, X., Carroni, M., Nussbaum‐Krammer, C., Mogk, A., Nillegoda, N. B., Szlachcic, A., Guilbride, D. L., Saibil, H. R., Mayer, M. P., & Bukau, B. (2015). Human Hsp70 Disaggregase reverses Parkinson's‐linked α‐Synuclein amyloid fibrils. Molecular Cell, 59, 781–793.
Han, S. K., Lee, D., Lee, H., Kim, D., Son, H. G., Yang, J. S., Lee, S. J. V., & Kim, S. (2016). OASIS 2: Online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research. Oncotarget, 7, 56147–56152.
Kamath, R. S., & Ahringer, J. (2003). Genome‐wide RNAi screening in Caenorhabditis elegans. Methods, 30, 313–321.
Kirstein, J., Arnsburg, K., Scior, A., Szlachcic, A., Guilbride, D. L., Morimoto, R. I., Bukau, B., & Nillegoda, N. B. (2017). In vivo properties of the disaggregase function of J‐proteins and Hsc70 in Caenorhabditis elegans stress and aging. Aging Cell, 16, 1414–1424.
Knobloch, M., Konietzko, U., Krebs, D. C., & Nitsch, R. M. (2007). Intracellular Abeta and cognitive deficits precede beta‐amyloid deposition in transgenic arcAbeta mice. Neurobiology of Aging, 28, 1297–1306.
Kreis, P., Gallrein, C., Rojas‐Puente, E., Mack, T. G. A., Kroon, C., Dinkel, V., Willmes, C., Murk, K., tom‐Dieck, S., Schuman, E. M., Kirstein, J., & Eickholt, B. J. (2019). ATM phosphorylation of the actin‐binding protein drebrin controls oxidation stress‐resistance in mammalian neurons and C. Elegans. Nature Communications, 10, 486.
Kuo, Y., Ren, S., Lao, U., Edgar, B. A., & Wang, T. (2013). Suppression of polyglutamine protein toxicity by co‐expression of a heat‐shock protein 40 and a heat‐shock protein 110. Cell Death & Disease, 4, e833.
LaFerla, F. M., Green, K. N., & Oddo, S. (2007). Intracellular amyloid‐beta in Alzheimer's disease. Nature Reviews. Neuroscience, 8, 499–509.
Malinverni, D., Zamuner, S., Rebeaud, M. E., Barducci, A., Nillegoda, N. B., & de Los Rios, P. (2023). Data‐driven large‐scale genomic analysis reveals an intricate phylogenetic and functional landscape in J‐domain proteins. Proceedings of the National Academy of Sciences, 120, e2218217120.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985). Amyloid plaque core protein in Alzheimer disease and down syndrome. Proceedings of the National Academy of Sciences of the United States of America, 82, 4245–4249.
Mello, C. C., Kramer, J. M., Stinchcomb, D., & Ambros, V. (1991). Efficient gene transfer in C. Elegans: extrachromosomal maintenance and integration of transforming sequences. The EMBO Journal, 10, 3959–3970.
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003). Triple‐transgenic model of Alzheimer's disease with plaques and tangles: Intracellular Abeta and synaptic dysfunction. Neuron, 39, 409–421.
Pigazzini, M. L., Gallrein, C., Iburg, M., Kaminski Schierle, G., & Kirstein, J. (2020). Characterization of amyloid structures in aging C. elegans using fluorescence lifetime imaging. Journal of Visualized Experiments. https://doi.org/10.3791/61004
Pigazzini, M. L., Lawrenz, M., Margineanu, A., Kaminski Schierle, G. S., & Kirstein, J. (2021). An expanded Polyproline domain maintains mutant huntingtin soluble in vivo and during aging. Frontiers in Molecular Neuroscience, 14, 721749.
Powers, E. T., Morimoto, R. I., Dillin, A., Kelly, J. W., & Balch, W. E. (2009). Biological and chemical approaches to diseases of proteostasis deficiency. Annual Review of Biochemistry, 78, 959–991.
Pras, A., Houben, B., Aprile, F. A., Seinstra, R.́., Gallardo, R., Janssen, L., Hogewerf, W., Gallrein, C., de Vleeschouwer, M., Mata‐Cabana, A., Koopman, M., Stroo, E., de Vries, M., Louise Edwards, S., Kirstein, J., Vendruscolo, M., Falsone, S. F., Rousseau, F., Schymkowitz, J., & Nollen, E. A. A. (2021). The cellular modifier MOAG‐4/SERF drives amyloid formation through charge complementation. The EMBO Journal, 40, e107568.
Rampelt, H., Kirstein‐Miles, J., Nillegoda, N. B., Chi, K., Scholz, S. R., Morimoto, R. I., & Bukau, B. (2012). Metazoan Hsp70 machines use Hsp110 to power protein disaggregation. The EMBO Journal, 31, 4221–4235.
Rampelt, H., Mayer, M. P., & Bukau, B. (2018). Nucleotide exchange factors for Hsp70 chaperones. Methods in Molecular Biology, 1709, 179–188.
Riera‐Tur, I., Schäfer, T., Hornburg, D., Mishra, A., da Silva Padilha, M., Fernández‐Mosquera, L., Feigenbutz, D., Auer, P., Mann, M., Baumeister, W., Klein, R., Meissner, F., Raimundo, N., Fernández‐Busnadiego, R., & Dudanova, I. (2022). Amyloid‐like aggregating proteins cause lysosomal defects in neurons via gain‐of‐function toxicity. Life Science Alliance, 5, e202101185.
Rosenzweig, R., Nillegoda, N. B., Mayer, M. P., & Bukau, B. (2019). The Hsp70 chaperone network. Nature Reviews. Molecular Cell Biology, 20, 665–680.
Scior, A., Buntru, A., Arnsburg, K., Ast, A., Iburg, M., Juenemann, K., Pigazzini, M. L., Mlody, B., Puchkov, D., Priller, J., Wanker, E. E., Prigione, A., & Kirstein, J. (2018). Complete suppression of Htt fibrilization and disaggregation of Htt fibrils by a trimeric chaperone complex. The EMBO Journal, 37, 282–299.
Song, Y., Nagy, M., Ni, W., Tyagi, N. K., Fenton, W. A., López‐Giráldez, F., Overton, J. D., Horwich, A. L., & Brady, S. T. (2013). Molecular chaperone Hsp110 rescues a vesicle transport defect produced by an ALS‐associated mutant SOD1 protein in squid axoplasm. Proceedings of the National Academy of Sciences of the United States of America, 110, 5428–5433.
Stroo, E., Koopman, M., Nollen, E. A. A., & Mata‐Cabana, A. (2017). Cellular regulation of amyloid formation in aging and disease. Frontiers in Neuroscience, 11, 64.
Taguchi, Y. V., Gorenberg, E. L., Nagy, M., Thrasher, D., Fenton, W. A., Volpicelli‐Daley, L., Horwich, A. L., & Chandra, S. S. (2019). Hsp110 mitigates α‐synuclein pathology in vivo. Proceedings of the National Academy of Sciences of the United States of America, 116, 24310–24316.
Tittelmeier, J., Sandhof, C. A., Ries, H. M., Druffel‐Augustin, S., Mogk, A., Bukau, B., & Nussbaum‐Krammer, C. (2020). The HSP110/HSP70 disaggregation system generates spreading‐competent toxic α‐synuclein species. The EMBO Journal, 39, e103954.
Warren, S. C., Margineanu, A., Alibhai, D., Kelly, D. J., Talbot, C., Alexandrov, Y., Munro, I., Katan, M., Dunsby, C., & French, P. M. W. (2013). Rapid global fitting of large fluorescence lifetime imaging microscopy datasets. PLoS One, 8, e70687.
Wentink, A., & Rosenzweig, R. (2023). Protein disaggregation machineries in the human cytosol. Current Opinion in Structural Biology, 83, 102735.
Yakubu, U. M., & Morano, K. A. (2021). Suppression of aggregate and amyloid formation by a novel intrinsically disordered region in metazoan Hsp110 chaperones. The Journal of Biological Chemistry, 296, 100567.