Signal Transduction of Doublecortin kinases

The goal of this project is to explore mechanisms of signaling to the microtubule (MT)-based-cytoskeleton. Doublecortin (DCX) is a novel microtubule associated protein (MAP) and is the major gene mutated in X-Lissencephaly and Subcortical Band Heterotopia (X-LIS /SCLH), a severe disorder in neuronal migration during development of the cerebral cortex. Doublecortin kinase 2 (DCK2) is a chimeric protein with a domain highly related to that of DCX fused to a protein kinase domain related to calmodulin-dependent protein kinases. The goal of this project is to investigate the functional effects and role of phosphorylation in the interaction of DCK2 with the MT-cytoskeleton, and to test the hypothesis that cellular events such as the establishment of neuronal polarity and neuronal process extension may be dependent upon rapid modulation of MT dynamics due to reversible signaling to and from members of the DCX/DCK family of proteins.