Noncanonical Modulation of the eIF2 Pathway Controls an Increase in Local Translation during Neural Wiring.
Mol Cell
; 73(3): 474-489.e5, 2019 02 07.
Article
em En
| MEDLINE
| ID: mdl-30595434
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 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 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-eIF2α 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.
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MEDLINE
Assunto principal:
Células Ganglionares da Retina
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Fator de Iniciação 2 em Eucariotos
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Fator de Iniciação 2B em Eucariotos
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Proteínas de Xenopus
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Neurogênese
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article