PXD058409

PXD058409 is an original dataset announced via ProteomeXchange.

Title	Distinct roles for MNK1 and MNK2 in social and cognitive behavior through kinase-specific regulation of the synaptic proteome and phosphoproteome
Description	Local mRNA translation is required for adaptive changes in the synaptic proteome. The mitogen-activated protein kinase (MAPK) interacting protein kinases 1 and 2 (MNK1 and MNK2) have emerged as key regulators of neuronal translation, primarily through phosphorylation of the eukaryotic initiation factor 4E (eIF4E). The therapeutic benefits of targeting the MNKs are being investigated for nervous system conditions and disorders that affect translation, including autism, pain, and cancer. However, it is still unclear if MNK1 and MNK2 regulate distinct aspects of neuronal translation and how the activity of each kinase is associated with the synaptic and behavioral features linked to MNK signaling. To examine the individual neurobiological functions of each kinase, we use knockout mice lacking either MNK1 or MNK2. We find that the knockout of MNK1 and MNK2 leads to different social and cognitive behavioral profiles and distinct alterations of the cortical synaptic proteome, transcriptome, and phosphoproteome. Loss of MNK1 is associated with an increase in ribosomal protein expression, whereas deletion of MNK2 decreases the expression of synaptic proteins. Phosphoproteome analysis suggests that MNK1 and MNK2 regulate largely distinct phosphorylation sites at the synapse, consistent with their differential effects on the synaptic proteome. Together, our findings provide evidence for a high degree of functional specialization of the MNKs in synaptic compartments and suggest that pharmacological inhibition of individual MNK may provide more specific targets for neurological disorders.
HostingRepository	PRIDE
AnnounceDate	2026-06-01
AnnouncementXML	Submission_2026-05-31_17:45:58.353.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Oliver Popp
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-29 04:55:09	ID requested
⏵ 1	2026-05-31 17:45:59	announced

Proce RO, Steinecker M, Giacomelli C, Uddstr, ö, m E, Chatterjee A, W, ü, sthoff S, Teixeira Alves LG, Popp O, Pohl T, Maxwell K, Hortmann L, Kunz S, Mertins P, Landthaler M, Bunina D, H, ö, rnberg H, Distinct roles for MNK1 and MNK2 in social and cognitive behavior through kinase-specific regulation of the synaptic proteome and phosphoproteome. Mol Psychiatry, 31(6):3446-3461(2026) [pubmed]

10.1038/s41380-026-03483-w;

submitter keyword: MNK1, TMT, synaptoneurosomes, MNK2

Hanna Hörnberg
contact affiliation	Max Delbrück Center for Molecular Medicine in the Helmholtz association (MDC) Robert-Rössle-Straße 10 13125 Berlin
contact email	Hanna.Hoernberg@mdc-berlin.de
lab head
Oliver Popp
contact affiliation	MDC Berlin
contact email	oliver.popp@mdc-berlin.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/2026/06/PXD058409

PRIDE project URI

• PRIDE
  1. PXD058409
     1. Label: PRIDE project
     2. Name: Distinct roles for MNK1 and MNK2 in social and cognitive behavior through kinase-specific regulation of the synaptic proteome and phosphoproteome