LIS1 regulates CNS lamination by interacting with mNudE, a central component of the centrosome

LIS1, a microtubule-associated protein, is required for neuronal migration, but the precise mechanism of LIS1 function is unknown. We identified a LIS 1 interacting protein encoded by a mouse homolog of NUDE, a nuclear distrib ution gene in A. nidulans and a multicopy suppressor of the LIS1 homolog, N UDF. mNudE is located in the centrosome or microtubule organizing center (M TOC), and interacts with six different centrosomal proteins. Overexpression of mNudE dissociates gamma -tubulin from the centrosome and disrupts micro tubule organization. Missense mutations that disrupt LIS1 function block LI S1-mNudE binding. Moreover, misexpression of the LIS1 binding domain of mNu dE in Xenopus embryos disrupts the architecture and lamination of the CNS. Thus, LIS1-mNudE interactions may regulate neuronal migration through dynam ic reorganization of the MTOC.