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Axonal ER tubules regulate local translation via P180/RRBP1-mediated ribosome interactions
Open accessPreprint — published as 10.1016/j.devcel.2024.05.005 · Paper page
Abstract
SUMMARY: Local mRNA translation in axons is critical for the spatial and temporal regulation of the axonal proteome. A wide variety of mRNAs are localized and translated in axons, however how protein synthesis is regulated at specific subcellular sites in axons remains unclear. Here, we establish that the axonal endoplasmic reticulum (ER) supports axonal translation. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with ER tubules in the axon in a translation-dependent manner and are influenced by specific extrinsic cues. We identify P180/RRBP1 as an axonally distributed ribosome receptor that regulates local translation in an mRNA-dependent manner. Our results establish an important role for the axonal ER in localizing mRNA translation and in dynamically regulating the axonal proteome in response to neuronal stimuli.
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Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
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Metadata
- Authors
- Koppers, M., Özkan, N., Nguyen, H. H., Jurriens, D., McCaughey, J., Stucchi, R., Altelaar, M., Kapitein, L. C., Hoogenraad, C. C., & Farias, G. G.
- Affiliations
- Utrecht University (NL)
- Genentech (US)
- Corresponding author
- Koppers, Max
- ORCID
- Venue
- Developmental Cell
- Publisher
- openRxiv
- Published
- 2022-12-01
- Volume
- 59
- Issue
- 16
- Pages
- 2053-2068.e9
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC11338522
- OpenAlex
- W4399123356
- Cited by
- 44
- References
- 1
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 7 · 2023: 1 · 2022: 1
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Developmental Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- VU Research Portal (submittedVersion, other-oa)
- Funders
- European Molecular Biology Organization
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.Veni.202.113, ALTF 741-2020, 016.Vidi.189.019)
- European Research Council
- H2020 European Research Council (ERC-CoG 819219, ERC-CoG 617050, ERC-StG 950617)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- ER tubules, ribosome distribution, axon development, axon morphology, hippocampal neurons, neuronal development
- MeSH terms
- Animals, Axons, Carrier Proteins, Cells, Cultured, Endoplasmic Reticulum, Hippocampus, Humans, Neurons, Ribosomal Proteins, Ribosomes, RNA, Messenger, Protein Biosynthesis, Rats
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