THE ROLE OF MAP KINASE-INTERACTING KINASES 1 AND 2 IN SYNAPTIC MORPHOLOGY

The MAP-kinase interacting kinases (MNKs) have been shown to act as important regulators of mRNA translation. Previous studies have shown that MNK1 and MNK2 have differing effects on the synaptic proteome. However, it is unclear how the two MNKs affect synaptic morphology and function. MNKs and their downstream targets have been implicated in the pathogenesis of several nervous system disorders, as well as other systemic conditions like cancers, infections, and pro-inflammatory states. This has made them an attractive subject of investigation as treatment targets. Understanding the specific roles of MNK1 and MNK2 in the brain may therefore bring us a step closer to developing new therapeutic approaches for conditions that affect translation.
Here, we provide preliminary evidence of structural differences in the knockout models of MNK1 and MNK2 at the synaptic level. Our lab has previously discovered structural differences in the post-synaptic densities in these knockout models, relative to wildtype. To explore structural effects in a more comprehensive manner, we analyzed 3D FIB-SEM image data using the open-source EspINA software. This approach allows detailed three-dimensional characterization of synaptic architecture, including density, surface area (synapse apposition surface) and the distribution of asymmetric and symmetric synapses. Ongoing analyses will enable systematic comparison of synaptic structural parameters, including synaptic mitochondria, between MNK1 and MNK2 knockout models.