Summary: They look nearly identical under a microscope, but two related enzymes, MNK1 and MNK2, play vastly different roles in shaping how we think and socialize. A study has revealed that these kinases act as “behavioral switches.” While MNK1 is essential for object recognition and memory, MNK2 regulates social curiosity and interaction.
The research shows that these enzymes fine-tune the production of proteins at the synapses—the communication points between neurons. This discovery could pave the way for highly precise therapies for neurological disorders, allowing doctors to target social deficits or memory loss individually.
Key Facts
- The MNK1 Memory Hub: Mice lacking MNK1 showed a significant loss of interest in new objects and impaired memory, linked to an overabundance of ribosomal proteins at the synapses.
- The MNK2 Social Switch: Mice without MNK2 appeared normal in memory tests but showed an enhanced interest in social contact, linked to reduced signaling proteins at the synapses.
- Synaptic Specificity: The molecular differences between the two kinases were far more pronounced at the synapses than in the rest of the brain, suggesting they specialize in local communication between neurons.
- Fine-Tuning Plasticity: Both enzymes regulate how mRNA is translated into proteins at the synapse, a process fundamental to “rewiring” the brain based on experience (synaptic plasticity).
- Targeted Drug Potential: Because the enzymes have distinct behavioral effects, future drugs could selectively inhibit one or the other to treat specific symptoms of autism, ADHD, or chronic pain.
Source: Helmholtz
Researchers at the Max Delbrück Center show that two related enzymes, MNK1 and MNK2, act on the brain to regulate different behaviors.
Their findings, published in “Molecular Psychiatry,” could help guide development of more precise therapies for neurological disorders.
Structurally, they look similar: MNK1 and MNK2 belong to the same enzyme family and are best known for regulating how cells make proteins. Their starring role in such a crucial cellular function has cast them into the spotlight as potential drug targets to treat nervous system disorders and chronic pain. But would it matter whether a drug targets only one of them?
In a study published in “Molecular Psychiatry,” researchers led by Rosalba Olga Proce, a doctoral student in the Molecular and Cellular Basis of Behavior lab led by Dr. Hanna Hörnberg at the Max Delbrück Center, set out to determine whether the two enzymes – also called kinases – perform distinct functions in the brain.
The team found clear differences. Mice lacking MNK1 showed less interest in newly introduced objects than controls and impaired memory of objects. By contrast, mice without MNK2 appeared normal in object recognition tests but showed enhanced interest in social contacts.
“The behavioral differences we observed suggest that each kinase has a specialized function,” says Proce. “It might be preferable to target each kinase individually when designing drugs.”
Mouse behavior and molecular data
To uncover how these behavioral changes arose, the researchers used genetically engineered mice in which either the MNK1 or MNK2 gene was knocked out. They then combined behavioral testing with large-scale molecular analyses of brain tissue.
The team focused in particular on the cerebral cortex and on synapses – contact points where neurons communicate. Using proteomics, transcriptomics, and phosphoproteomics, they compared protein levels, gene expression, and protein phosphorylation patterns between the two types of mice.
Mice lacking MNK1 had an abundance of ribosomal proteins, which play a central role in transcribing messenger RNA into proteins. By contrast, in mice lacking MNK2, the expression and phosphorylation of proteins responsible for transmitting messages in synapses was reduced.
Notably, the researchers found that the molecular differences between the two kinases were far more pronounced in synapses than in whole-brain samples.
“We were surprised to see these differences,” says Hörnberg. “This suggest that the kinases may have different functions in the cell body compared to synapses.”
Toward more selective therapies
Instead of broadly inhibiting both kinases, future therapies might selectively target one kinase or the other to achieve more specific effects, Hörnberg adds.
She and her colleagues now aim to identify other molecules with which MNK1 and MNK2 interact. They also plan to study in greater detail, how these kinases regulate translation of messenger RNA into proteins during synaptic plasticity – the strengthening or weakening of connections between neurons over time. Synaptic plasticity is the fundamental mechanism underlying learning and memory – enabling the brain to rewire itself based on experience.
By clarifying how protein synthesis is fine-tuned at synapses, the team hopes to lay the groundwork for more precise interventions in neurological and psychiatric disorders.
Key Questions Answered:
A: Not quite, but they govern different aspects of your behavior. MNK1 helps your brain keep track of the physical world and new objects (memory), while MNK2 acts as a filter for your social appetite.
A: MNK kinases are already known to be involved in how the nervous system processes pain signals. Knowing that MNK1 and MNK2 have such different effects on the brain means we can design pain relievers that don’t accidentally mess with your memory or social life.
A: Since MNK2 specifically regulates interest in social contacts, it is a prime candidate for future research into social-related disorders like autism or extreme social anxiety. The goal is to “fine-tune” these switches to help the brain respond more appropriately to social stimuli.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuroscience research news
Author: Gunjan Sinha
Source: Helmholtz
Contact: Gunjan Sinha – Helmholtz
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Distinct roles for MNK1 and MNK2 in social and cognitive behavior through kinase-specific regulation of the synaptic proteome and phosphoproteome” by Rosalba Olga Proce, Maria Steinecker, Chiara Giacomelli, Erika Uddström, Anirban Chatterjee, Souhaila Wüsthoff, Luiz Gustavo Teixeira Alves, Oliver Popp, Tobias Pohl, Katie Maxwell, Lucie Hortmann, Severine Kunz, Philipp Mertins, Markus Landthaler, Daria Bunina & Hanna Hörnberg. Molecular Psychiatry
DOI:10.1038/s41380-026-03483-w
Abstract
Distinct roles for MNK1 and MNK2 in social and cognitive behavior through kinase-specific regulation of the synaptic proteome and phosphoproteome
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 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 used knockout mice lacking either MNK1 or MNK2. We found that 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 was associated with increased ribosomal protein expression, whereas deletion of MNK2 decreased the expression and phosphorylation of synaptic proteins.
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 MNKs may provide more specific targets for neurological disorders.
