Axonal endoplasmic reticulum tubules control local translation via P180/RRBP1-mediated ribosome interactions

Max Koppers; Nazmiye Özkan; Ha H Nguyen; Daphne Jurriens; Janine McCaughey; Dan T M Nguyen; Chun Hei Li; Riccardo Stucchi; Maarten Altelaar; Harold D MacGillavry; Lukas C Kapitein; Casper C Hoogenraad; Ginny G Farías

doi:10.1016/j.devcel.2024.05.005

Axonal endoplasmic reticulum tubules control local translation via P180/RRBP1-mediated ribosome interactions

Max Koppers, Nazmiye Özkan, Ha H Nguyen, Daphne Jurriens, Janine McCaughey, Dan T M Nguyen, Chun Hei Li, Riccardo Stucchi, Maarten Altelaar, Harold D MacGillavry, Lukas C Kapitein, Casper C Hoogenraad, Ginny G Farías

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Local mRNA translation in axons is critical for the spatiotemporal 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 in developing rat hippocampal cultured neurons. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with axonal ER tubules 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 and binds to mRNAs enriched for axonal membrane proteins. Importantly, the impairment of axonal ER-ribosome interactions causes defects in axon morphology. Our results establish a role for the axonal ER in dynamically localizing mRNA translation, which is important for proper neuron development.

Original language	English
Pages (from-to)	2053-2068.e9
Journal	Developmental Cell
Volume	59
Issue number	16
DOIs	https://doi.org/10.1016/j.devcel.2024.05.005
Publication status	Published - 19 Aug 2024

Bibliographical note

Funding

This work was supported by the Netherlands Organization of Scientific Research ( VI.VENI.202.113 ) to M.K., EMBO long-term fellowship ( ALTF 741-2020 ) to J.M., European Research Council ( ERC-CoG 819219 ) to L.C.K., European Research Council ( ERC-CoG 617050 ) to C.C.H., European Research Council ( ERC-StG 950617 ) to G.G.F., and Netherlands Organization of Scientific Research ( 0.16.VIDI.189.019 ) to G.G.F. This work was supported by the Netherlands Organization of Scientific Research (VI.VENI.202.113) to M.K. EMBO long-term fellowship (ALTF 741-2020) to J.M. European Research Council (ERC-CoG 819219) to L.C.K. European Research Council (ERC-CoG 617050) to C.C.H. European Research Council (ERC-StG 950617) to G.G.F. and Netherlands Organization of Scientific Research (0.16.VIDI.189.019) to G.G.F. Conceptualization, M.K. and G.G.F.; methodology, M.K. N.O. H.H.N. H.D.M. and G.G.F.; investigation, M.K. N.O. H.H.N. D.J. J.M. D.T.M.N. C.H.L. and R.S.; formal analysis, M.K. N.O. H.H.N. and D.J.; visualization, M.K. H.H.N. and N.O.; supervision, G.G.F. M.K. H.D.M. L.C.K. M.A. and C.C.H.; writing \u2013 original draft, M.K. and G.G.F.; and writing \u2013 review & editing, M.K. G.G.F. N.O. H.H.N. and C.C.H. C.C.H. is an employee of Genentech, a member of the Roche group.

Funders	Funder number
European Molecular Biology Organization
European Research Council	0.16, ERC-CoG 617050, ERC-StG 950617, ERC-CoG 819219
European Research Council
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	VI.VENI.202.113, ALTF 741-2020
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Keywords

Animals
Endoplasmic Reticulum/metabolism
Ribosomes/metabolism
Axons/metabolism
Rats
Protein Biosynthesis
RNA, Messenger/genetics
Hippocampus/metabolism
Neurons/metabolism
Cells, Cultured
Ribosomal Proteins/metabolism
Humans

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10.1016/j.devcel.2024.05.005

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Koppers, M., Özkan, N., Nguyen, H. H., Jurriens, D., McCaughey, J., Nguyen, D. T. M., Li, C. H., Stucchi, R., Altelaar, M., MacGillavry, H. D., Kapitein, L. C., Hoogenraad, C. C., & Farías, G. G. (2024). Axonal endoplasmic reticulum tubules control local translation via P180/RRBP1-mediated ribosome interactions. Developmental Cell, 59(16), 2053-2068.e9. https://doi.org/10.1016/j.devcel.2024.05.005

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abstract = "Local mRNA translation in axons is critical for the spatiotemporal 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 in developing rat hippocampal cultured neurons. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with axonal ER tubules 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 and binds to mRNAs enriched for axonal membrane proteins. Importantly, the impairment of axonal ER-ribosome interactions causes defects in axon morphology. Our results establish a role for the axonal ER in dynamically localizing mRNA translation, which is important for proper neuron development.",

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Koppers, M, Özkan, N, Nguyen, HH, Jurriens, D, McCaughey, J, Nguyen, DTM, Li, CH, Stucchi, R, Altelaar, M, MacGillavry, HD, Kapitein, LC, Hoogenraad, CC & Farías, GG 2024, 'Axonal endoplasmic reticulum tubules control local translation via P180/RRBP1-mediated ribosome interactions', Developmental Cell, vol. 59, no. 16, pp. 2053-2068.e9. https://doi.org/10.1016/j.devcel.2024.05.005

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T1 - Axonal endoplasmic reticulum tubules control local translation via P180/RRBP1-mediated ribosome interactions

AU - Koppers, Max

AU - Özkan, Nazmiye

AU - Nguyen, Ha H

AU - Jurriens, Daphne

AU - McCaughey, Janine

AU - Nguyen, Dan T M

AU - Li, Chun Hei

AU - Stucchi, Riccardo

AU - Altelaar, Maarten

AU - MacGillavry, Harold D

AU - Kapitein, Lukas C

AU - Hoogenraad, Casper C

AU - Farías, Ginny G

PY - 2024/8/19

Y1 - 2024/8/19

N2 - Local mRNA translation in axons is critical for the spatiotemporal 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 in developing rat hippocampal cultured neurons. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with axonal ER tubules 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 and binds to mRNAs enriched for axonal membrane proteins. Importantly, the impairment of axonal ER-ribosome interactions causes defects in axon morphology. Our results establish a role for the axonal ER in dynamically localizing mRNA translation, which is important for proper neuron development.

AB - Local mRNA translation in axons is critical for the spatiotemporal 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 in developing rat hippocampal cultured neurons. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with axonal ER tubules 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 and binds to mRNAs enriched for axonal membrane proteins. Importantly, the impairment of axonal ER-ribosome interactions causes defects in axon morphology. Our results establish a role for the axonal ER in dynamically localizing mRNA translation, which is important for proper neuron development.

KW - Animals

KW - Endoplasmic Reticulum/metabolism

KW - Ribosomes/metabolism

KW - Axons/metabolism

KW - Rats

KW - Protein Biosynthesis

KW - RNA, Messenger/genetics

KW - Hippocampus/metabolism

KW - Neurons/metabolism

KW - Cells, Cultured

KW - Ribosomal Proteins/metabolism

KW - Humans

U2 - 10.1016/j.devcel.2024.05.005

DO - 10.1016/j.devcel.2024.05.005

M3 - Article

C2 - 38815583

SN - 1534-5807

VL - 59

SP - 2053-2068.e9

JO - Developmental Cell

JF - Developmental Cell

IS - 16

ER -

Axonal endoplasmic reticulum tubules control local translation via P180/RRBP1-mediated ribosome interactions

Abstract

Bibliographical note

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Keywords

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