RT Journal Article
SR Electronic
T1 Nwd1 regulates neuronal differentiation and migration through purinosome formation in the developing cerebral cortex
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2019.12.15.877340
DO 10.1101/2019.12.15.877340
A1 Seiya Yamada
A1 Ayaka Sato
A1 Shin-ichi Sakakibara
YR 2019
UL http://biorxiv.org/content/early/2019/12/16/2019.12.15.877340.abstract
AB Engagement of neural stem/progenitor cells (NSPCs) into proper neuronal differentiation requires the spatiotemporally regulated generation of metabolites. Purines are essential building blocks for many signaling molecules. Enzymes that catalyze de novo purine synthesis are assembled as a huge multienzyme complex called “purinosome.” However, there is no evidence of the formation or physiological function of the purinosome in the brain. Here, we showed that a signal transduction ATPases with numerous domains (STAND) protein, NACHT and WD repeat domain-containing 1 (Nwd1), interacted with Paics, a purine-synthesizing enzyme, to regulate purinosome assembly in NSPCs. Altered Nwd1 expression affected purinosome formation and induced the mitotic exit and premature differentiation of NSPCs, repressing neuronal migration and periventricular heterotopia. Overexpression/knockdown of Paics or Fgams, other purinosome enzymes, in the developing brain resulted in a phenocopy of Nwd1 defects. These findings indicate that strict regulation of purinosome assembly/disassembly is crucial for maintaining NSPCs and corticogenesis.