Hook3 interacts with PCM1 to regulate pericentriolar material assembly and the timing of neurogenesis

Abstract

Centrosome functions are important in many brain developmental processes. Proper functioning of the centrosome relies on assembly of protein components into the pericentriolar material. This dynamic assembly is mediated by the trafficking of pericentriolar satellites, which are comprised of centrosomal proteins. Here we demonstrate that trafficking of pericentriolar satellites requires the interaction between Hook3 and Pericentriolar Material 1 (PCM1). Hook3, previously shown to link the centrosome and the nucleus in C. elegans, is recruited to pericentriolar satellites through interaction with PCM1, a protein associated with schizophrenia. Knocking down of Hook3 or PCM1, or disrupting the Hook3-PCM1 interaction in vivo impairs interkinetic nuclear migration, a featured behavior of embryonic neural progenitors. This in turn leads to overproduction of neurons and premature depletion of the neural progenitor pool in the developing neocortex. These results underscore the importance of centrosomal assembly in neurogenesis, and provide potential insights into the etiology of brain developmental diseases related to centrosome dysfunction.