Dataset Information

Distinct roles for MNK1 and MNK2 in social and cognitive behavior through kinase-specific regulation of the synaptic proteome and phosphoproteome

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Oliver Popp

LAB HEAD: Hanna Hörnberg

PROVIDER: PXD058409 | Pride | 2026-06-01

REPOSITORIES: Pride

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			Action	DRS
	Rowlf_20221007_OP_MMtmtpro_Hahoe_MNKs_Batch1_Plex1_GP_fr01.raw	Raw
	Rowlf_20221007_OP_MMtmtpro_Hahoe_MNKs_Batch1_Plex1_GP_fr02.raw	Raw
	Rowlf_20221007_OP_MMtmtpro_Hahoe_MNKs_Batch1_Plex1_GP_fr03.raw	Raw
	Rowlf_20221007_OP_MMtmtpro_Hahoe_MNKs_Batch1_Plex1_GP_fr04.raw	Raw
	Rowlf_20221007_OP_MMtmtpro_Hahoe_MNKs_Batch1_Plex1_GP_fr05.raw	Raw

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Distinct roles for MNK1 and MNK2 in social and cognitive behavior through kinase-specific regulation of the synaptic proteome and phosphoproteome.

Proce Rosalba Olga RO Steinecker Maria M Giacomelli Chiara C Uddström Erika E Chatterjee Anirban A Wüsthoff Souhaila S Teixeira Alves Luiz Gustavo LG Popp Oliver O Pohl Tobias T Maxwell Katie K Hortmann Lucie L Kunz Severine S Mertins Philipp P Landthaler Markus M Bunina Daria D Hörnberg Hanna H

Molecular psychiatry 20260213 6

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 that affect translation, including autism and pain. However, it is still unclear if ...[more]

PMID: 41688788

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