Dataset Information

Cue-induced modulation of eIF2α-eIF2Bε underlies axonal translation up-regulation in neural wiring

ABSTRACT: Local protein synthesis is rapidly regulated by extrinsic signals during neural wiring but the translational control mechanisms remain elusive. Here, we show that the guidance cue Sema3A, but not Slit1, elicits precise spatiotemporal control of the phosphorylation of the translation initiation factor, eIF2α, in axonal growth cones via the Unfolded Protein Response (UPR) kinase PERK. Strikingly, in contrast to the canonical UPR signaling, we find that the Sema3A-induced eIF2α phosphorylation bypasses the conventional global translational repression and underlies a burst in axonal protein synthesis, mediated by differential eIF2B activity. Ultrasensitive proteomics on somaless axons reveals a subset of 75 proteins translationally regulated via Sema3A-p-eIF2α, including several proteostasis- and actin cytoskeleton-related nascent proteins. Finally, in vivo experiments provide evidence that eIF2α phosphorylation drives the formation of the retinotectal axon projection. Thus, specific extracellular cues can trigger non-canonical PERK-eIF2α-eIF2B signaling leading to subcellular dynamic remodeling of the nascent proteome required for neural wiring.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Xenopus Laevis (african Clawed Frog)

SUBMITTER: Christian Frese

LAB HEAD: Jeroen Krijgsveld

PROVIDER: PXD009250 | Pride | 2019-01-02

REPOSITORIES: pride

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Dataset's files

Source:

			Action	DRS
	20160114_CF_axon_pSILAC_isrib_A.raw	Raw
	20160114_CF_axon_pSILAC_isrib_B.raw	Raw
	20160114_CF_axon_pSILAC_isrib_C.raw	Raw
	20160114_CF_axon_pSILAC_sema_isrib_A.raw	Raw
	20160114_CF_axon_pSILAC_sema_isrib_B.raw	Raw

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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]

PMID: 30595434

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