The architecture of protein synthesis in the developing neocortex at near-atomic resolution reveals Ebp1-mediated neuronal proteostasis at the 60S tunnel exit
| Item Type: | Preprint |
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| Title: | The architecture of protein synthesis in the developing neocortex at near-atomic resolution reveals Ebp1-mediated neuronal proteostasis at the 60S tunnel exit |
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| Creators Name: | Kraushar, M.L. and Krupp, F. and Turko, P. and Ambrozkiewicz, M.C. and Sprink, T. and Imami, K. and Vieira-Vieira, C.H. and Schaub, T. and Harnett, D. and Münster-Wandowski, A. and Bürger, J. and Zinnall, U. and Borisova, E. and Yamamoto, H. and Rasin, M.R. and Beule, D. and Landthaler, M. and Mielke, T. and Tarabykin, V. and Vida, I. and Selbach, M. and Spahn, C.M.T. |
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| Abstract: | Protein synthesis must be finely tuned in the nervous system, as it represents an essential feature of neurodevelopmental gene expression, and dominant pathology in neurological disease. However, the architecture of ribosomal complexes in the developing mammalian brain has not been analyzed at high resolution. This study investigates the architecture of ribosomes ex vivo from the embryonic and perinatal mouse neocortex, revealing Ebp1 as a 60S peptide tunnel exit binding factor at near-atomic resolution by multiparticle cryo-electron microscopy. The impact of Ebp1 on the neuronal proteome was analyzed by pSILAC and BONCAT coupled mass spectrometry, implicating Ebp1 in neurite outgrowth proteostasis, with in vivo embryonic Ebp1 knockdown resulting in dysregulation of neurite outgrowth. Our findings reveal Ebp1 as a central component of neocortical protein synthesis, and the 60S peptide tunnel exit as a focal point of gene expression control in the molecular specification of neuronal morphology. |
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| Keywords: | Ebp1, Ribosome, Proteostasis, Brain, Neocortex, Neurons, Development, Cryo-EM, pSILAC, BONCAT |
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| Source: | bioRxiv |
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| Publisher: | Cold Spring Harbor Laboratory Press |
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| Article Number: | 2020.02.08.939488 |
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| Date: | 10 February 2020 |
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| Official Publication: | https://doi.org/10.1101/2020.02.08.939488 |
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| Related to: | |
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