Mutations in Doublecortin cause Lissencephaly (smooth brain), a neuronal migration disorder characterized by epilepsy and mental retardation (1). Doublecortin is a microtubule associated protein that stabilizes and bundles microtubules. A conserved doublecortin domain mediates the interaction with microtubules, and interestingly most missense mutations cluster in this domain (2). Kinases JNK, CDK5 and PKA phosphorylate doublecortin. JNK phosphorylates Thr321, Thr331 and Ser334 while PKA phosphorylates Ser47 and CDK5 phosphorylates Ser297 (3-5). Phosphorylation of Ser297 lowers the affinity of doublecortin to microtubules. Furthermore, mutations of Ser297 result in migration defects (5).
