Summary: Two closely related enzymes, MNK1 and MNK2, look almost identical under the microscope but play very different roles in shaping cognition and social behavior. New research shows these kinases act like behavioral switches: MNK1 is crucial for object recognition and memory, while MNK2 influences social curiosity and interaction. The study reveals that both enzymes fine-tune local protein production at synapses—the sites where neurons communicate—pointing to the possibility of more selective therapies for neurological and psychiatric disorders.
Researchers found that MNK1 and MNK2 differentially regulate the synaptic proteome and phosphoproteome, altering how mRNA is translated into proteins at neuronal connections. These synapse-specific effects suggest therapeutic strategies could selectively target one kinase to treat particular symptoms, such as memory impairment or social deficits, while minimizing off-target consequences.
Key Facts
- MNK1 and memory: Mice lacking MNK1 showed reduced interest in novel objects and impaired object memory, associated with an increased abundance of ribosomal proteins at synapses.
- MNK2 and social behavior: Mice lacking MNK2 performed normally in object recognition but displayed an increased drive for social contact, linked to decreased levels and phosphorylation of synaptic signaling proteins.
- Synaptic specificity: Differences between MNK1 and MNK2 were much more pronounced in synaptic fractions than in whole-brain samples, indicating localized specialization at neuronal connections.
- Regulation of translation: Both kinases influence local mRNA translation at synapses, a central mechanism for synaptic plasticity—the strengthening or weakening of connections that underlies learning and memory.
- Targeted drug potential: Because each kinase produces distinct behavioral outcomes, developing selective MNK1- or MNK2-focused drugs could allow clinicians to treat cognitive, social, or pain-related symptoms more precisely.
Source: Helmholtz
Summary of the study
A team at the Max Delbrück Center, led by Dr. Hanna Hörnberg with doctoral researcher Rosalba Olga Proce, investigated whether MNK1 and MNK2 have distinct functions in the brain. Their findings, published in Molecular Psychiatry, provide evidence that the two kinases play specialized roles in behavior by regulating the synaptic proteome and phosphoproteome.
Behavioral tests and molecular profiling in mice
To determine how each kinase affects behavior, the researchers used genetically engineered mice lacking either MNK1 or MNK2. They combined behavioral assays with large-scale molecular analyses of cortical tissue, focusing on synapses. Using proteomics, transcriptomics, and phosphoproteomics, they compared protein abundance, gene expression, and phosphorylation patterns across genotypes.
The MNK1-deficient mice displayed reduced exploratory interest in novel objects and deficits in object recognition memory. Molecular profiling revealed an overrepresentation of ribosomal proteins at synaptic sites, consistent with altered translational capacity. In contrast, MNK2-deficient mice showed unchanged object memory but an increased preference for social contact; their synaptic proteome exhibited reduced levels and phosphorylation of proteins involved in synaptic signaling.
Importantly, these molecular differences were far more pronounced at synapses than in whole-brain samples, indicating that MNK1 and MNK2 exert specialized, localized effects on the translation machinery and signaling networks that support synaptic function and plasticity.
Implications for selective therapies
The distinct behavioral and molecular profiles produced by loss of MNK1 versus MNK2 suggest that selectively targeting one kinase could yield therapeutic benefits with fewer side effects than broad MNK inhibition. For example, selectively inhibiting MNK2 might modulate social behavior without impairing memory, whereas targeting MNK1 could influence memory-related processes without altering social drives.
The researchers plan to map additional interaction partners for each kinase and to study in more detail how MNK1 and MNK2 regulate translation during synaptic plasticity. A deeper understanding of how protein synthesis is tuned at synapses may provide a rational basis for developing drugs aimed at specific cognitive or social symptoms in conditions such as autism spectrum disorders, attention-deficit disorders, chronic pain, and other neurological or psychiatric disorders.
Key questions answered
A: Not exactly. MNK1 and MNK2 influence different behavioral domains. MNK1 supports memory for objects and the physical environment, while MNK2 helps regulate social motivation. They modulate different aspects of brain function rather than creating global traits.
A: MNK kinases are involved in neuronal translation and signaling pathways that affect how pain signals are processed. Understanding the distinct roles of MNK1 and MNK2 raises the possibility of pain treatments that spare cognitive or social functions by selectively targeting one kinase.
A: MNK2 is a promising candidate for research into social behavior interventions because its absence specifically increased social interest in mice. Future studies will be needed to determine whether and how MNK2-targeted approaches could help people with social anxiety or autism-related social challenges.
Editorial notes
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full by staff editors.
- Additional context was supplied by the editorial team.
About this neuroscience research news
Author: Gunjan Sinha
Source: Helmholtz
Contact: Gunjan Sinha – Helmholtz
Image credit: 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 — 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 supports adaptive changes in the synaptic proteome. The mitogen-activated protein kinase (MAPK)–interacting kinases MNK1 and MNK2 have emerged as important regulators of neuronal translation, notably through phosphorylation of the eukaryotic initiation factor eIF4E. Targeting MNKs is being evaluated for conditions that affect translation, including autism and chronic pain. However, whether MNK1 and MNK2 differentially control neuronal translation and how each kinase relates to synaptic and behavioral features associated with MNK signaling remained unclear.
To probe their individual roles, the study examined knockout mice lacking either MNK1 or MNK2. Loss of each kinase produced distinct social and cognitive behavioral profiles and unique alterations in the cortical synaptic proteome, transcriptome, and phosphoproteome. MNK1 deletion correlated with increased ribosomal protein expression, while MNK2 deletion reduced the abundance and phosphorylation of synaptic proteins. Together, these findings indicate a high degree of functional specialization of MNKs at synapses and suggest that pharmacological inhibition of individual MNKs may offer more specific targets for neurological disorders.