Unknown

Dataset Information

0

Noncanonical Modulation of the eIF2 Pathway Controls an Increase in Local Translation during Neural Wiring.


ABSTRACT: Local translation is rapidly regulated by extrinsic signals during neural wiring, but its control mechanisms remain elusive. Here we show that the extracellular cue Sema3A induces an initial burst in local translation that precisely controls phosphorylation of the translation initiation factor eIF2? via the unfolded protein response (UPR) kinase PERK. Strikingly, in contrast to canonical UPR signaling, Sema3A-induced eIF2? phosphorylation bypasses global translational repression and underlies an increase in local translation through differential activity of eIF2B mediated by protein phosphatase 1. Ultrasensitive proteomics analysis of axons reveals 75 proteins translationally controlled via the Sema3A-p-eIF2? pathway. These include proteostasis- and actin cytoskeleton-related proteins but not canonical stress markers. Finally, we show that PERK signaling is needed for directional axon migration and visual pathway development in vivo. Thus, our findings reveal a noncanonical eIF2 signaling pathway that controls selective changes in axon translation and is required for neural wiring.

SUBMITTER: Cagnetta R 

PROVIDER: S-EPMC6375727 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Noncanonical Modulation of the eIF2 Pathway Controls an Increase in Local Translation during Neural Wiring.

Cagnetta Roberta R   Wong Hovy Ho-Wai HH   Frese Christian K CK   Mallucci Giovanna R GR   Krijgsveld Jeroen J   Holt Christine E CE  

Molecular cell 20181227 3


Local translation is rapidly regulated by extrinsic signals during neural wiring, but its control mechanisms remain elusive. Here we show that the extracellular cue Sema3A induces an initial burst in local translation that precisely controls phosphorylation of the translation initiation factor eIF2α via the unfolded protein response (UPR) kinase PERK. Strikingly, in contrast to canonical UPR signaling, Sema3A-induced eIF2α phosphorylation bypasses global translational repression and underlies an  ...[more]

Similar Datasets

2019-01-02 | PXD009250 | Pride
| S-EPMC6838152 | biostudies-literature
2014-03-15 | E-GEOD-55420 | biostudies-arrayexpress
| S-EPMC3725134 | biostudies-literature
| S-EPMC6501578 | biostudies-literature
| S-EPMC3006201 | biostudies-literature
| S-EPMC3513554 | biostudies-literature
| S-EPMC3189197 | biostudies-literature
| S-EPMC3435221 | biostudies-other
| S-EPMC4271102 | biostudies-other