Reelin plays an important role in normal formation of the cortical layer during brain development and synaptic plasticity in adult brain. In reelin signaling, tyrosine phosphorylation functions importantly in many processes including phosphorylation of intracellular adaptor protein Disabled-1 by Src family kinase leading to enhancement of long-term potentiation, a proposed cellular correlate to memory and learning.
Twinfilin1 (TWF1), an actin-monomer-binding protein, is composed of two actin depolymerizing factor (ADF)-homology domains. It plays an important role in the regulation of actin dynamics by inhibiting nucleotide exchange on actin monomers and preventing assembly of the monomer into filaments. Our previous studies have found that tyrosine phosphorylation level of TWF1 was decreased in reelin mutant mice. Besides, we found that TWF1 was phosphorylated by Src mainly at the position of tyrosine 309. Therefore, we have hypothesized that tyrosine phosphorylation of TWF1 may be involved in reelin signaling to process synaptic plasticity. To test this working hypothesis, we have generated a mouse line in the C57BL/6J strain with TWF1 gene mutation (TWF1-Y309F), in which phosphorylation on the tyrosine 309 site was inhibited.  
In the present study, we analyzed the behavioral phenotypes of TWF1-Y309F mice by using touchscreen-based visual discrimination (VD) task and other general behavioral tests. As results, we found some cognitive deficits in TWF1-Y309F mice both in the fear conditioning test and VD task. These results suggest that tyrosine phosphorylation of TWF1 is involved in processing cognition, learning and memory.