Hook3 interacts with PCM1 to regulate pericentriolar material assembly and the timing of neurogenesis.
Centrosome functions are important in multiple 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. Disruption of 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 the centrosome dysfunction.
Picower Institute for Learning and Memory, Department of Brain and Cognitive, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 46, Room 4235A, Cambridge, MA 02139, USA.
Xuecai
X
Ge
Christopher L
CL
Frank
Froylan
F
Calderon de Anda
Li-Huei
LH
Tsai
D000818:Animals; D001324:Autoantigens / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology; D018385:Centrosome / Q000378:metabolism / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D041681:NIH 3T3 Cells; D055495:Neurogenesis / Q000502:physiology*; D011247:Pregnancy; D011485:Protein Binding / Q000502:physiology; D013234:Stem Cells / Q000502:physiology; D013997:Time Factors
D001324:Autoantigens; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; C086074:PCM1 protein, human; C425466:hook3 protein, human