Local translatome sustains synaptic function in impaired Wallerian degeneration.
Antennal Grooming Behavior
Local mRNA Translation
Programmed Axon Degeneration
Synaptic Function
Wallerian Degeneration
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
31 Oct 2024
31 Oct 2024
Historique:
received:
10
02
2024
accepted:
17
10
2024
revised:
07
10
2024
medline:
1
11
2024
pubmed:
1
11
2024
entrez:
1
11
2024
Statut:
aheadofprint
Résumé
After injury, severed axons separated from their somas activate programmed axon degeneration, a conserved pathway to initiate their degeneration within a day. Conversely, severed projections deficient in programmed axon degeneration remain morphologically preserved with functional synapses for weeks to months after axotomy. How this synaptic function is sustained remains currently unknown. Here, we show that dNmnat overexpression attenuates programmed axon degeneration in distinct neuronal populations. Severed projections remain morphologically preserved for weeks. When evoked, they elicit a postsynaptic behavior, a readout for preserved synaptic function. We used ribosomal pulldown to isolate the translatome from these projections 1 week after axotomy. Translatome candidates of enriched biological classes identified by transcriptional profiling are validated in a screen using a novel automated system to detect evoked antennal grooming as a proxy for preserved synaptic function. RNAi-mediated knockdown reveals that transcripts of the mTORC1 pathway, a mediator of protein synthesis, and of candidate genes involved in protein ubiquitination and Ca
Identifiants
pubmed: 39482489
doi: 10.1038/s44319-024-00301-8
pii: 10.1038/s44319-024-00301-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)
ID : 176855
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)
ID : 211015
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)
ID : 190919
Organisme : International Foundation for Research in Paraplegia (IRP)
ID : P180
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 23K27107
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : GR20107
Informations de copyright
© 2024. The Author(s).
Références
Alvarez J (2001) The autonomous axon: a model based on local synthesis of proteins. Biol Res. https://doi.org/10.4067/S0716-97602001000200014
Anders S, Pyl PT, Huber W (2015) HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics 31:166–169
doi: 10.1093/bioinformatics/btu638
pubmed: 25260700
Bittner GD (1988) Long term survival of severed distal axonal stumps in vertebrates and invertebrates. Integr Comp Biol 28:1165–1179. https://doi.org/10.1093/icb/28.4.1165
doi: 10.1093/icb/28.4.1165
Bittner GD (1991) Long-term survival of anucleate axons and its implications for nerve regeneration. Trends Neurosci 14:188–193. https://doi.org/10.1016/0166-2236(91)90104-3
doi: 10.1016/0166-2236(91)90104-3
pubmed: 1713720
Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114–2120. https://doi.org/10.1093/bioinformatics/btu170
doi: 10.1093/bioinformatics/btu170
pubmed: 24695404
pmcid: 4103590
Brazill JM, Li C, Zhu Y, Zhai RG (2017) NMNAT: It’s an NAD+ synthase… It’s a chaperone… It’s a neuroprotector. Curr Opin Genet Dev 44:156–162. https://doi.org/10.1016/j.gde.2017.03.014
doi: 10.1016/j.gde.2017.03.014
pubmed: 28445802
Coleman MP, Höke A (2020) Programmed axon degeneration: from mouse to mechanism to medicine. Nat Rev Neurosci 21:183–196. https://doi.org/10.1038/s41583-020-0269-3
doi: 10.1038/s41583-020-0269-3
pubmed: 32152523
Court FA, Hendriks WTJ, MacGillavry HD, Alvarez J, Van Minnen J (2008) Schwann cell to axon transfer of ribosomes: toward a novel understanding of the role of glia in the nervous system. J Neurosci 28:11024–11029. https://doi.org/10.1523/JNEUROSCI.2429-08.2008
doi: 10.1523/JNEUROSCI.2429-08.2008
pubmed: 18945910
Danecek P, Bonfield JK, Liddle J, Marshall J, Ohan V, Pollard MO, Whitwham A, Keane T, McCarthy SA, Davies RM, Li H (2021) Twelve years of SAMtools and BCFtools. Gigascience. 10:giab008
Ding Q, Cecarini V, Keller JN (2007) Interplay between protein synthesis and degradation in the CNS: physiological and pathological implications. Trends Neurosci 30:31–36. https://doi.org/10.1016/j.tins.2006.11.003
doi: 10.1016/j.tins.2006.11.003
pubmed: 17126920
Ederle H, Dormann D (2017) TDP-43 and FUS en route from the nucleus to the cytoplasm. FEBS Lett 591:1489–1507. https://doi.org/10.1002/1873-3468.12646
doi: 10.1002/1873-3468.12646
pubmed: 28380257
Essuman K, Summers DW, Sasaki Y, Mao X, DiAntonio A, Milbrandt J (2017) The SARM1 toll/interleukin-1 receptor domain possesses intrinsic NAD+ cleavage activity that promotes pathological axonal degeneration. Neuron 93:1334–1343.e5. https://doi.org/10.1016/j.neuron.2017.02.022
doi: 10.1016/j.neuron.2017.02.022
pubmed: 28334607
Fang Y, Soares L, Teng X, Geary M, Bonini NM (2012) A novel drosophila model of nerve injury reveals an essential role of Nmnat in maintaining axonal integrity. Curr Biol 22:590–595. https://doi.org/10.1016/j.cub.2012.01.065
doi: 10.1016/j.cub.2012.01.065
pubmed: 22425156
Gerdts J, Brace EJ, Sasaki Y, DiAntonio A, Milbrandt J (2015) SARM1 activation triggers axon degeneration locally via NAD+ destruction. Science 348:453–457. https://doi.org/10.1126/science.1258366
doi: 10.1126/science.1258366
pubmed: 25908823
Gilley J, Coleman MP (2010) Endogenous Nmnat2 is an essential survival factor for maintenance of healthy axons. PLoS Biol 8:e1000300. https://doi.org/10.1371/journal.pbio.1000300
doi: 10.1371/journal.pbio.1000300
pubmed: 20126265
Glock C, Biever A, Tushev G, Nassim-Assir B, Kao A, Bartnik I, tom Dieck S Schuman EM (2021) The translatome of neuronal cell bodies, dendrites, and axons. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.2113929118
Hampel S, Franconville R, Simpson JH, Seeds AM (2015) A neural command circuit for grooming movement control. Elife. https://doi.org/10.7554/eLife.08758
Hampel S, McKellar CE, Simpson JH, Seeds AM (2017) Simultaneous activation of parallel sensory pathways promotes a grooming sequence in drosophila. Elife. https://doi.org/10.7554/eLife.28804
Holt CE, Martin KC, Schuman EM (2019) Local translation in neurons: visualization and function. Nat Struct Mol Biol 26:557–566. https://doi.org/10.1038/s41594-019-0263-5
doi: 10.1038/s41594-019-0263-5
pubmed: 31270476
Hu Y, Flockhart I, Vinayagam A, Bergwitz C, Berger B, Perrimon N, Mohr SE (2011) An integrative approach to ortholog prediction for disease-focused and other functional studies. BMC Bioinforma 12:357. https://doi.org/10.1186/1471-2105-12-357
doi: 10.1186/1471-2105-12-357
Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57. https://doi.org/10.1038/nprot.2008.211
doi: 10.1038/nprot.2008.211
pubmed: 19131956
Ishiguro A, Kimura N, Watanabe Y, Watanabe S, Ishihama A (2016) TDP-43 binds and transports G-quadruplex-containing mRNAs into neurites for local translation. Genes Cells 21:466–481. https://doi.org/10.1111/gtc.12352
doi: 10.1111/gtc.12352
pubmed: 26915990
Iwata A, Stys PK, Wolf JA, Chen XH, Taylor AG, Meaney DF, Smith DH (2004) Traumatic axonal injury induces proteolytic cleavage of the voltage-gated sodium channels modulated by tetrodotoxin and protease inhibitors. J Neurosci 24:4605–4613. https://doi.org/10.1523/JNEUROSCI.0515-03.2004
doi: 10.1523/JNEUROSCI.0515-03.2004
pubmed: 15140932
Jarome TJ, Helmstetter FJ (2014) Protein degradation and protein synthesis in long-term memory formation. Front Mol Neurosci. https://doi.org/10.3389/fnmol.2014.00061
Jung H, Yoon BC, Holt CE (2012) Axonal mRNA localization and local protein synthesis in nervous system assembly, maintenance and repair. Nat Rev Neurosci 13:597. https://doi.org/10.1038/nrn3210
doi: 10.1038/nrn3210
Jung J, Ohk J, Kim H, Holt CE, Park HJ, Jung H (2023) mRNA transport, translation, and decay in adult mammalian central nervous system axons. Neuron 111:650–668.e4. https://doi.org/10.1016/j.neuron.2022.12.015
doi: 10.1016/j.neuron.2022.12.015
pubmed: 36584679
Kim D, Langmead B, Salzberg SL (2015) HISAT: a fast spliced aligner with low memory requirements. Nat Methods 12:357–360. https://doi.org/10.1038/nmeth.3317
doi: 10.1038/nmeth.3317
pubmed: 25751142
Larsson MC, Domingos AI, Jones WD, Chiappe ME, Amrein H, Vosshall LB (2004) Or83b encodes a broadly expressed odorant receptor essential for Drosophila olfaction. Neuron 43:703–714. https://doi.org/10.1016/j.neuron.2004.08.019
doi: 10.1016/j.neuron.2004.08.019
pubmed: 15339651
Lee T, Luo L (1999) Mosaic analysis with a repressible neurotechnique cell marker for studies of gene function in neuronal morphogenesis. Neuron 22:451–461. https://doi.org/10.1016/S0896-6273(00)80701-1
doi: 10.1016/S0896-6273(00)80701-1
pubmed: 10197526
Llobet Rosell A, Neukomm LJ (2019) Axon death signalling in Wallerian degeneration among species and in disease. Open Biol. https://doi.org/10.1098/rsob.190118
Llobet Rosell A, Paglione M, Gilley J, Kocia M, Perillo G, Gasparrini M, Cialabrini L, Raffaelli N, Angeletti C, Orsomando G, Wu PH, Coleman MP, Loreto A, Neukomm LJ (2022) The NAD+ precursor NMN activates dSarm to trigger axon degeneration in Drosophila. Elife. https://doi.org/10.7554/ELIFE.80245
Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550. https://doi.org/10.1186/s13059-014-0550-8
doi: 10.1186/s13059-014-0550-8
pubmed: 25516281
Lunn ER, Perry VH, Brown MC, Rosen H, Gordon S (1989) Absence of Wallerian degeneration does not hinder regeneration in peripheral nerve. Eur J Neurosci 1:27–33. https://doi.org/10.1111/j.1460-9568.1989.tb00771.x
doi: 10.1111/j.1460-9568.1989.tb00771.x
pubmed: 12106171
MacDonald JM, Beach MG, Porpiglia E, Sheehan AE, Watts RJ, Freeman MR (2006) The Drosophila cell corpse engulfment receptor Draper mediates glial clearance of severed axons. Neuron 50:869–881. https://doi.org/10.1016/j.neuron.2006.04.028
doi: 10.1016/j.neuron.2006.04.028
pubmed: 16772169
Mack TGA, Reiner M, Beirowski B, Mi W, Emanuelli M, Wagner D, Thomson D, Gillingwater T, Court F, Conforti L, Fernando FS, Tarlton A, Andressen C, Addicks K, Magni G, Ribchester RR, Perry VH, Coleman MP (2001) Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nat Neurosci 4:1199–1206. https://doi.org/10.1038/nn770
doi: 10.1038/nn770
pubmed: 11770485
Neukomm LJ, Burdett TC, Gonzalez MA, Züchner S, Freeman MR (2014) Rapid in vivo forward genetic approach for identifying axon death genes in Drosophila. Proc Natl Acad Sci USA 111:9965–9970. https://doi.org/10.1073/pnas.1406230111
doi: 10.1073/pnas.1406230111
pubmed: 24958874
Neukomm LJ, Burdett TC, Seeds AM, Hampel S, Coutinho-Budd JC, Farley JE, Wong J, Karadeniz YB, Osterloh JM, Sheehan AE, Freeman MR (2017) Axon death pathways converge on axundead to promote functional and structural axon disassembly. Neuron 95:78–91.e5. https://doi.org/10.1016/j.neuron.2017.06.031
doi: 10.1016/j.neuron.2017.06.031
pubmed: 28683272
Niou ZX, S Yang, A Sri, H Rodriquez, J Gilley, MP Coleman, H-C Lu (2022) NMNAT2 in cortical glutamatergic neurons exerts both cell and non-cell autonomous influences to shape cortical development and to maintain neuronal health. Preprint at https://doi.org/10.1101/2022.02.05.479195
Osterloh JM, Yang J, Rooney TM, Fox AN, Adalbert R, Powell EH, Sheehan AE, Avery MA, Hackett R, Logan MA, MacDonald JM, Ziegenfuss JS, Milde S, Hou YJ, Nathan C, Ding A, Brown RH, Conforti L, Coleman M, Tessier-Lavigne M, Züchner S, Freeman MR (2012) dSarm/Sarm1 is required for activation of an injury-induced axon death pathway. Science 337:481–484. https://doi.org/10.1126/science.1223899
doi: 10.1126/science.1223899
pubmed: 22678360
Ostroff LE, Santini E, Sears R, Deane Z, Kanadia RN, Ledoux JE, Lhakhang T, Tsirigos A, Heguy A, Klann E (2019) Axon TRAP reveals learning-associated alterations in cortical axonal mRNAs in the lateral amgydala. Elife. https://doi.org/10.7554/eLife.51607
Paglione M, Rosell AL, Chatton JY, Neukomm LJ (2020) Morphological and functional evaluation of axons and their synapses during axon death in Drosophila melanogaster. J Vis Exp. https://doi.org/10.3791/60865
Polilov AA (2012) The smallest insects evolve anucleate neurons. Arthropod Struct Dev 41:29–34. https://doi.org/10.1016/j.asd.2011.09.001
doi: 10.1016/j.asd.2011.09.001
pubmed: 22078364
Polilov AA (2017) Anatomy of adult Megaphragma (Hymenoptera: Trichogrammatidae), one of the smallest insects, and new insight into insect miniaturization. PLoS ONE 12:e0175566. https://doi.org/10.1371/journal.pone.0175566
doi: 10.1371/journal.pone.0175566
pubmed: 28467417
Raiders S, Han T, Scott-Hewitt N, Kucenas S, Lew D, Logan MA, Singhvi A (2021) Engulfed by glia: glial pruning in development, function, and injury across species. J Neurosci 41:823–833. https://doi.org/10.1523/JNEUROSCI.1660-20.2020
doi: 10.1523/JNEUROSCI.1660-20.2020
pubmed: 33468571
Rishal I, Fainzilber M (2014) Axon-soma communication in neuronal injury. Nat Rev Neurosci 15:32–42. https://doi.org/10.1038/nrn3609
doi: 10.1038/nrn3609
pubmed: 24326686
Rozenbaum M, Rajman M, Rishal I, Koppel I, Koley S, Medzihradszky KF, Oses-Prieto JA, Kawaguchi R, Amieux PS, Burlingame AL, Coppola G, Fainzilber M (2018) Translatome regulation in neuronal injury and axon regrowth. eNeuro 5:ENEURO.0276-17.2018. https://doi.org/10.1523/ENEURO.0276-17.2018
doi: 10.1523/ENEURO.0276-17.2018
pubmed: 29756027
Sapar ML, Han C (2019) Die in pieces: how Drosophila sheds light on neurite degeneration and clearance. J Genet Genomics 46:187–199. https://doi.org/10.1016/j.jgg.2019.03.010
doi: 10.1016/j.jgg.2019.03.010
pubmed: 31080046
Stirling DP, Stys PK (2010) Mechanisms of axonal injury: internodal nanocomplexes and calcium deregulation. Trends Mol Med 16:160–170. https://doi.org/10.1016/j.molmed.2010.02.002
doi: 10.1016/j.molmed.2010.02.002
pubmed: 20207196
Terenzio M, Koley S, Samra N, Rishal I, Zhao Q, Sahoo PK, Urisman A, Marvaldi L, Oses-Prieto JA, Forester C, Gomes C, Kalinski AL, Di Pizio A, Doron-Mandel E, Perry RBT, Koppel I, Twiss JL, Burlingame AL, Fainzilber M (2018) Locally translated mTOR controls axonal local translation in nerve injury. Science 359:1416–1421. https://doi.org/10.1126/science.aan1053
doi: 10.1126/science.aan1053
pubmed: 29567716
Thelen MP, Kye MJ (2020) The role of RNA binding proteins for local mRNA translation: implications in neurological disorders. Front Mol Biosci. https://doi.org/10.3389/fmolb.2019.00161
Thomas A, Lee PJ, Dalton JE, Nomie KJ, Stoica L, Costa-Mattioli M, Chang P, Nuzhdin S, Arbeitman MN, Dierick HA (2012) A versatile method for cell-specific profiling of translated mRNAs in Drosophila. PLoS ONE 7:e40276. https://doi.org/10.1371/journal.pone.0040276
doi: 10.1371/journal.pone.0040276
pubmed: 22792260
Vosshall LB, Wong AM, Axel R (2000) An olfactory sensory map in the fly brain. Cell 102:147–159. https://doi.org/10.1016/S0092-8674(00)00021-0
doi: 10.1016/S0092-8674(00)00021-0
pubmed: 10943836
Waller AV (1850) XX. Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibres. Philos Trans R Soc Lond 140:423–429. https://doi.org/10.1098/rstl.1850.0021
doi: 10.1098/rstl.1850.0021
Wang JW, Wong AM, Flores J, Vosshall LB, Axel R (2003) Two-photon calcium imaging reveals an odor-evoked map of activity in the fly brain. Cell 112:271–282. https://doi.org/10.1016/S0092-8674(03)00004-7
doi: 10.1016/S0092-8674(03)00004-7
pubmed: 12553914
Xiong X, Hao Y, Sun K, Li J, Li X, Mishra B, Soppina P, Wu C, Hume RI, Collins CA (2012) The highwire ubiquitin ligase promotes axonal degeneration by tuning levels of Nmnat protein. PLoS Biol 10:e1001440. https://doi.org/10.1371/journal.pbio.1001440
doi: 10.1371/journal.pbio.1001440
pubmed: 23226106
Yamaguchi M, Lee I, Jantrapirom S, Suda K, Yoshida H (2021) Drosophila models to study causative genes for human rare intractable neurological diseases. Exp Cell Res 403:112584. https://doi.org/10.1016/j.yexcr.2021.112584
doi: 10.1016/j.yexcr.2021.112584
pubmed: 33812867
Yamaguchi M, Takashima H (2018) Drosophila charcot-marie-tooth disease models. In: Yamaguchi M (ed) Advances in experimental medicine and biology. pp 97–117. https://doi.org/10.1007/978-981-13-0529-0_7
Yang J, Wu Z, Renier N, Simon DJ, Uryu K, Park DS, Greer PA, Tournier C, Davis RJ, Tessier-Lavigne M (2015) Pathological axonal death through a Mapk cascade that triggers a local energy deficit. Cell 160:161–176. https://doi.org/10.1016/j.cell.2014.11.053
doi: 10.1016/j.cell.2014.11.053
pubmed: 25594179
Yoon BC, Jung H, Dwivedy A, O'Hare CM, Zivraj KH, Holt CE (2012) Local translation of extranuclear lamin B promotes axon maintenance. Cell 148:752–764. https://doi.org/10.1016/j.cell.2011.11.064
doi: 10.1016/j.cell.2011.11.064
pubmed: 22341447
Zhai RG, Cao Y, Hiesinger PR, Zhou Y, Mehta SQ, Schulze KL, Verstreken P, Bellen HJ (2006) Drosophila NMNAT maintains neural integrity independent of its NAD synthesis activity. PLoS Biol 4:e416. https://doi.org/10.1371/journal.pbio.0040416
doi: 10.1371/journal.pbio.0040416
pubmed: 17132048
Zhai RG, Rizzi M, Garavaglia S (2009) Nicotinamide/nicotinic acid mononucleotide adenylyltransferase, new insights into an ancient enzyme. Cell Mol Life Sci 66:2805–2818. https://doi.org/10.1007/s00018-009-0047-x
doi: 10.1007/s00018-009-0047-x
pubmed: 19448972
Zhang K, Coyne AN, Lloyd TE (2018) Drosophila models of amyotrophic lateral sclerosis with defects in RNA metabolism. Brain Res 1693:109–120. https://doi.org/10.1016/j.brainres.2018.04.043
doi: 10.1016/j.brainres.2018.04.043
pubmed: 29752901
Zhulyn O, Rosenblatt HD, Shokat L, Dai S, Kuzuoglu-Öztürk D, Zhang Z, Ruggero D, Shokat KM, Barna M (2023) Evolutionarily divergent mTOR remodels translatome for tissue regeneration. Nature 620:163–171. https://doi.org/10.1038/s41586-023-06365-1
doi: 10.1038/s41586-023-06365-1
pubmed: 37495694