In vitro studies indicate a role for the LIM kinase family in the regulation of cofilin phosphorylation and actin dynamics. In addition, abnormal expression of LIMK-1 is associated with Williams syndrome, a mental disorder with profound deficits in visuospatial cognition. However, the in vivo function of this family of kinases remains elusive. Using LIMK-1 knockout mice, we demonstrate a significant role for LIMK-1 in vivo in regulating cofilin and the actin cytoskeleton. Furthermore, we show that the knockout mice exhibited significant abnormalities in spine morphology and in synaptic function, including enhanced hippocampal long-term potentiation. The knockout mice also showed altered fear responses and spatial learning. These results indicate that LIMK-1 plays a critical role in dendritic spine morphogenesis and brain function.
Meng, Y., Zhang, Y., Tregoubov, V., Janus, C., Cruz, L., Jackson, M., … Jia, Z. (2002). Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice. Neuron, 35(1), 121–133. https://doi.org/10.1016/S0896-6273(02)00758-4