SDCCAG8 regulates pericentriolar material recruitment and neuronal migration in the developing cortex.

ABSTRACT

Mutations of SDCCAG8 are associated with nephronophthisis and Bardet-Biedl syndrome, as well as schizophrenia; however, the function of SDCCAG8 remains largely unknown. Here, we show that SDCCAG8 regulates centrosomal accumulation of pericentriolar material and neuronal polarization and migration in the developing mouse cortex. Sdccag8 expression is selectively elevated in newborn neurons prior to their commencement of radial locomotion, and suppression of this expression by short-hairpin RNAs or a loss-of-function allele impairs centrosomal recruitment of γ-tubulin and pericentrin, interferes with microtubule organization, decouples the centrosome and the nucleus, and disrupts neuronal migration. Moreover, SDCCAG8 interacts and cotraffics with pericentriolar material 1 (PCM1), a centriolar satellite protein crucial for targeting proteins to the centrosome. Expression of SDCCAG8 carrying a human mutation causes neuronal migration defects. These results reveal a critical role for SDCCAG8 in controlling centrosomal properties and function, and provide insights into the basis of neurological defects linked to SDCCAG8 mutations.