ADAM10-Initiated Release of Notch Intracellular Domain Regulates Microtubule Stability and Radial Migration of Cortical Neurons.

ABSTRACT: Proper neuronal migration is orchestrated by combined membrane signal paradigms, whereas the role and mechanism of regulated intramembrane proteolysis (RIP) remain to be illustrated. We show here that the disintegrin and metalloprotease-domain containing protein 10 (ADAM10) regulates cortical neurons migration by initiating the RIP of Notch. We found that Notch intracellular domain (NICD) significantly rescued the migration defect of ADAM10-deficient neurons. Moreover, ADAM10 deficiency led to reduced neuronal motility and disrupted microtubule (MT) structure, which were associated with downregulated expression of acetylated tubulin and MT-associated proteins. Specifically, the NICD/RBPJ complex bound directly to the promoter, and regulated the neuronal expression level of doublecortin (DC

SUBMITTER: Yang Z 

PROVIDER: S-EPMC6093323 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature