RAB6 and dynein drive post-Golgi apical transport to prevent neuronal progenitor delamination

EMBO Rep. 2022 Oct 6;23(10):e54605. doi: 10.15252/embr.202254605. Epub 2022 Aug 18.

Abstract

Radial glial (RG) cells are the neural stem cells of the developing neocortex. Apical RG (aRG) cells can delaminate to generate basal RG (bRG) cells, a cell type associated with human brain expansion. Here, we report that aRG delamination is regulated by the post-Golgi secretory pathway. Using in situ subcellular live imaging, we show that post-Golgi transport of RAB6+ vesicles occurs toward the minus ends of microtubules and depends on dynein. We demonstrate that the apical determinant Crumbs3 (CRB3) is also transported by dynein. Double knockout of RAB6A/A' and RAB6B impairs apical localization of CRB3 and induces a retraction of aRG cell apical process, leading to delamination and ectopic division. These defects are phenocopied by knockout of the dynein activator LIS1. Overall, our results identify a RAB6-dynein-LIS1 complex for Golgi to apical surface transport in aRG cells, and highlights the role of this pathway in the maintenance of neuroepithelial integrity.

Keywords: RAB6; cell polarity; dynein; neocortex development; polarized trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dyneins* / genetics
  • Dyneins* / metabolism
  • Golgi Apparatus / metabolism
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism
  • Neurons / metabolism
  • rab GTP-Binding Proteins* / genetics
  • rab GTP-Binding Proteins* / metabolism

Substances

  • Microtubule-Associated Proteins
  • Dyneins
  • rab GTP-Binding Proteins