PXD001074

PXD001074 is an original dataset announced via ProteomeXchange.

Title	BDNF stimulation of protein synthesis in cortical neurons requires the eIF4E kinase Mnk1
Description	Although the Mnks have been known for >15 years, their roles in the regulation of protein synthesis have remained obscure. Here we explore how BDNF stimulates protein synthesis in cortical neurons. Using a combination of pharmacological and genetic approaches, we show that this effect depends on MEK/ERK signaling and on the downstream kinase, Mnk1, which phosphorylates eIF4E. Translation initiation is mediated by the interaction of eIF4E with the m7GTP cap of mRNA and with eIF4G. The latter interaction is inhibited by the interactions of eIF4E with partner proteins such as CYFIP1, which together with its partner, FMRP acts as a translational repressor. We find that BDNF induces the release of CYFIP1 from eIF4E, and that this depends on Mnk1. Finally, using a novel combination of BONCAT and SILAC, we identify the a subset of proteins whose synthesis is upregulated by BDNF signalling via Mnk1 in neurons. The This subset of Mnk1-sensitive proteins are enriched for functions involved in neurotransmission and synaptic plasticity. Additionally, we find significant overlap between our subset of Mnk1 Mnk1-sensitive proteins and proteins encoded by known FMRP-binding mRNAs. Taken together, our data implicate Mnk1 as a key component of BDNF-mediated translational regulation in neurons.
HostingRepository	PRIDE
AnnounceDate	2014-11-06
AnnouncementXML	Submission_2015-06-01_06:46:08.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Harvey Johnston
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	deamidated residue; monohydroxylated residue; phosphorylated residue; iodoacetamide derivatized residue; 6x(13)C labeled residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2014-06-20 07:35:47	ID requested
1	2014-11-06 01:52:54	announced
⏵ 2	2015-06-01 06:46:09	announced	Updated publication reference for PubMed record(s): 25609615.

Genheden M, Kenney JW, Johnston HE, Manousopoulou A, Garbis SD, Proud CG, BDNF stimulation of protein synthesis in cortical neurons requires the MAP kinase-interacting kinase MNK1. J Neurosci, 35(3):972-84(2015) [pubmed]

curator keyword: Biomedical, Biological

submitter keyword: Mouse, Cortical neurons, BDNF, Mnk1, eIF4e, FMRP, BONCAT, SILAC, Obitrap Elite

Spiro D. Garbis
contact affiliation	Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK
contact email	s.d.garbis@soton.ac.uk
lab head
Harvey Johnston
contact affiliation	University of Southampton
contact email	h.johnston@soton.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001074
     1. Label: PRIDE project
     2. Name: BDNF stimulation of protein synthesis in cortical neurons requires the eIF4E kinase Mnk1