PreprintCited by 44RNA and protein synthesis mechanismsRNA Research and SplicingGenetics and Neurodevelopmental Disorders

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Axonal ER tubules regulate local translation via P180/RRBP1-mediated ribosome interactions

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Preprint — 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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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
Venue
Developmental Cell
Publisher
openRxiv
Published
2022-12-01
Volume
59
Issue
16
Pages
2053-2068.e9
ISSN
1534-5807 (ISSN-L)
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
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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