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

被引:20
作者
Brault, Jean-Baptiste [1 ]
Bardin, Sabine [1 ]
Lampic, Marusa [1 ]
Carpentieri, Jacopo A. [1 ]
Coquand, Laure [1 ,2 ]
Penisson, Maxime [2 ,3 ,4 ]
Lachuer, Hugo [1 ]
Victoria, Guiliana Soraya [1 ]
Baloul, Sarah [1 ]
El Marjou, Fatima [1 ]
Boncompain, Gaelle [1 ]
Miserey-Lenkei, Stephanie [1 ]
Belvindrah, Richard [2 ,3 ,4 ]
Fraisier, Vincent [5 ]
Francis, Fiona [2 ,3 ,4 ]
Perez, Franck [1 ]
Goud, Bruno [1 ]
Baffet, Alexandre D. [1 ,6 ]
机构
[1] PSL Res Univ, Inst Curie, CNRS UMR144, Paris, France
[2] Sorbonne Univ, Paris, France
[3] INSERM, UMR S 1270, Paris, France
[4] Inst Fer Moulin, Paris, France
[5] Inst Curie, Cell & Tissue Imaging Facil PICT IBiSA, UMR 144, CNRS, Paris, France
[6] Inst Natl Sante & Rech Med INSERM, Paris, France
关键词
cell polarity; dynein; neocortex development; polarized trafficking; RAB6; OUTER SUBVENTRICULAR ZONE; EPITHELIAL-CELL POLARITY; CYTOPLASMIC DYNEIN; NUCLEAR MIGRATION; RADIAL GLIA; DYNACTIN; RECRUITMENT; NEOCORTEX; MEMBRANE; GENE;
D O I
10.15252/embr.202254605
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:15
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