What We Know and Would Like to Know about CDKL5 and Its Involvement in Epileptic Encephalopathy

Figure 4

A model depicting the different functions of CDKL5 in the cytoplasmic and nuclear compartments. As described in the text, CDKL5 functions are occurring both in the cytoplasm and in the nucleus. A. In the cytoplasm, CDKL5 is involved in the regulation of actin cytoskeleton and dendritic arborization. This function is mediated by the interaction of CDKL5 with Rac1. Importantly, a link between BDNF, CDKL5 phosphorylation, and Rac1 activation has been suggested by Chen et al. [24]. B. In the cytoplasmic compartment, the levels of CDKL5 are regulated by degradation. Furthermore, we assume that several phosphorylation targets of CDKL5 remain to be identified. C. In the nucleus, CDKL5 has been proposed capable of interacting with and phosphorylating MeCP2 and DNMT1, thereby influencing gene expression and DNA methylation. Furthermore, the protein has been shown to colocalize with RNA speckles involved in RNA splicing. As for the cytosol, we assume that several other targets of CDKL5 remain to be discovered. In this model, we have neglected the capability of the nuclear CDKL5 to influence dendritic arborization [24] and the transcriptional regulation of CDKL5.