TY - JOUR T1 - The architecture of protein synthesis in the developing neocortex at near-atomic resolution reveals Ebp1-mediated neuronal proteostasis at the 60S tunnel exit JF - bioRxiv DO - 10.1101/2020.02.08.939488 SP - 2020.02.08.939488 AU - Matthew L. Kraushar AU - Ferdinand Krupp AU - Paul Turko AU - Mateusz C. Ambrozkiewicz AU - Thiemo Sprink AU - Koshi Imami AU - Carlos H. Vieira-Vieira AU - Theres Schaub AU - Dermot Harnett AU - Agnieszka Münster-Wandowski AU - Jörg Bürger AU - Ulrike Zinnall AU - Ekaterina Borisova AU - Hiroshi Yamamoto AU - Mladen-Roko Rasin AU - Dieter Beule AU - Markus Landthaler AU - Thorsten Mielke AU - Victor Tarabykin AU - Imre Vida AU - Matthias Selbach AU - Christian M.T. Spahn Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/02/10/2020.02.08.939488.abstract N2 - 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. ER -