DISC1 Regulates Neurogenesis via Modulating Kinetochore Attachment of Ndel1/Nde1 during Mitosis.

ABSTRACT: Mutations of DISC1 (disrupted-in-schizophrenia 1) have been associated with major psychiatric disorders. Despite the hundreds of DISC1-binding proteins reported, almost nothing is known about how DISC1 interacts with other proteins structurally to impact human brain development. Here we solved the high-resolution structure of DISC1 C-terminal tail in complex with its binding domain of Ndel1. Mechanistically, DISC1 regulates Ndel1's kinetochore attachment, but not its centrosome localization, during mitosis. Functionally, disrupting DISC1/Ndel1 complex formation prolongs mitotic length and interferes with cell-cycle progression in human cells, and it causes cell-cycle deficits of radial glial cells in the embryonic mouse cortex and human forebrain organoids. We also observed similar deficit

SUBMITTER: Ye F 

PROVIDER: S-EPMC5731645 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature