RT Journal Article
SR Electronic
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
FD Cold Spring Harbor Laboratory
SP 2020.02.08.939488
DO 10.1101/2020.02.08.939488
A1 Matthew L. Kraushar
A1 Ferdinand Krupp
A1 Paul Turko
A1 Mateusz C. Ambrozkiewicz
A1 Thiemo Sprink
A1 Koshi Imami
A1 Carlos H. Vieira-Vieira
A1 Theres Schaub
A1 Dermot Harnett
A1 Agnieszka Münster-Wandowski
A1 Jörg Bürger
A1 Ulrike Zinnall
A1 Ekaterina Borisova
A1 Hiroshi Yamamoto
A1 Mladen-Roko Rasin
A1 Dieter Beule
A1 Markus Landthaler
A1 Thorsten Mielke
A1 Victor Tarabykin
A1 Imre Vida
A1 Matthias Selbach
A1 Christian M.T. Spahn
YR 2020
UL http://biorxiv.org/content/early/2020/02/10/2020.02.08.939488.abstract
AB 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.