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Protein synthesis in the developing neocortex at near-atomic resolution reveals Ebp1-mediated neuronal proteostasis at the 60S tunnel exit

Item Type:Article
Title:Protein synthesis in the developing neocortex at near-atomic resolution reveals Ebp1-mediated neuronal proteostasis at the 60S tunnel exit
Creators Name:Kraushar, M.L. and Krupp, F. and Harnett, D. and Turko, P. and Ambrozkiewicz, M.C. and Sprink, T. and Imami, K. and Günnigmann, M. and Zinnall, U. and Vieira-Vieira, C.H. and Schaub, T. and Münster-Wandowski, A. and Bürger, J. and Borisova, E. and Yamamoto, H. and Rasin, M.R. and Ohler, U. and Beule, D. and Mielke, T. and Tarabykin, V. and Landthaler, M. and Kramer, G. and Vida, I. and Selbach, M. and Spahn, C.M.T.
Abstract:Protein synthesis must be finely tuned in the developing nervous system as the final essential step of gene expression. This study investigates the architecture of ribosomes from the neocortex during neurogenesis, revealing Ebp1 as a high-occupancy 60S peptide tunnel exit (TE) factor during protein synthesis at near-atomic resolution by cryoelectron microscopy (cryo-EM). Ribosome profiling demonstrated Ebp1-60S binding is highest during start codon initiation and N-terminal peptide elongation, regulating ribosome occupancy of these codons. Membrane-targeting domains emerging from the 60S tunnel, which recruit SRP/Sec61 to the shared binding site, displace Ebp1. Ebp1 is particularly abundant in the early-born neural stem cell (NSC) lineage and regulates neuronal morphology. Ebp1 especially impacts the synthesis of membrane-targeted cell adhesion molecules (CAMs), measured by pulsed stable isotope labeling by amino acids in cell culture (pSILAC)/bioorthogonal noncanonical amino acid tagging (BONCAT) mass spectrometry (MS). Therefore, Ebp1 is a central component of protein synthesis, and the ribosome TE is a focal point of gene expression control in the molecular specification of neuronal morphology during development.
Keywords:Ebp1, Ribosome, Proteostasis, Neocortex, Neurons, Development, Cryo-EM, pSILAC/BONCAT Mass Spectrometry, Ribosome Profiling, Selective Ribosome Profiling, Animals, Mice
Source:Molecular Cell
ISSN:1097-2765
Publisher:Cell Press
Date:22 December 2020
Official Publication:https://doi.org/10.1016/j.molcel.2020.11.037
PubMed:View item in PubMed

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