Spatiotemporal expression of Nischarin in developing rat brain mediates neuronal migration via the PAK1/LIMK1/cofilin pathway

Nischarin, a cytoplasmic scaffold protein, plays a crucial role in modulating cell morphology and function. Our prior investigations revealed its high expression in certain areas of the adult rat brain. Yet, the intricate spatiotemporal dynamics of Nischarin expression across various stages of rat development, as well as its influence on the nervous system’s functionality, remain unexplored. In this study, we meticulously examined the expression patterns of Nischarin and the phosphorylation profiles of the PAK1/LIMK1/cofilin signaling cascade within the cerebral cortex and hippocampus, spanning from embryonic development through postnatal maturation. Furthermore, we delved into how Nischarin affects the neuronal migration and the underlying mechanisms. Our findings indicated that from postnatal day 1 to 28, there was a consistent increasing trend in both the protein and mRNA levels of Nischarin in the cerebral cortex and hippocampus. Interestingly, the phosphorylation levels of PAK1 and LIMK1 increased briefly at postnatal day 1, and then gradually decreased from postnatal day 21 to 28. Immunocoprecipitation revealed the interaction between endogenous Nischarin and PAK1/LIMK1 in the cerebral cortex. Notably, suppressing Nischarin expression markedly bolstered the migration ability of Neuro-2a cells and concurrently elevated the phosphorylation levels of the PAK1/LIMK1/cofilin signaling pathway. This elevation was effectively counteracted by the PAK1 inhibitor IPA3. Our research suggests that the progressive increase in Nischarin protein expression during development is likely integral to the normal developmental trajectory of the rat brain. This involvement appears to be mediated by Nischarin’s regulation of neuronal migration through modulating the activity of the PAK1/LIMK1/cofilin signaling pathway.