PXD009250

PXD009250 is an original dataset announced via ProteomeXchange.

Title	Cue-induced modulation of eIF2α-eIF2Bε underlies axonal translation up-regulation in neural wiring
Description	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.
HostingRepository	PRIDE
AnnounceDate	2019-01-02
AnnouncementXML	Submission_2019-01-02_05:38:16.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Frese
SpeciesList	scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-19 01:15:44	ID requested
⏵ 1	2019-01-02 05:38:17	announced

Cagnetta R, Wong HH, Frese CK, Mallucci GR, Krijgsveld J, Holt CE, Noncanonical Modulation of the eIF2 Pathway Controls an Increase in Local Translation during Neural Wiring. Mol Cell, 73(3):474-489.e5(2019) [pubmed]

curator keyword: Biological

submitter keyword: pSILAC, axon, neuroproteomics

Jeroen Krijgsveld
contact affiliation	Division Proteomics of Stem Cells and Cancer (B230), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany
contact email	j.krijgsveld@dkfz.de
lab head
Christian Frese
contact affiliation	CECAD Research Center Cologne
contact email	cfrese@uni-koeln.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/01/PXD009250

PRIDE project URI

• PRIDE
  1. PXD009250
     1. Label: PRIDE project
     2. Name: Cue-induced modulation of eIF2α-eIF2Bε underlies axonal translation up-regulation in neural wiring