Biology subjects

Viais, R.

Publications and source records attributed to Viais, R..

2 recordsLinked to original sources

bioRxiv2020

Sub-centrosomal mapping identifies augmin-γTuRC as part of a centriole-stabilizing scaffold

Centriole biogenesis and maintenance are crucial for cells to generate cilia and assemble centrosomes that function as microtubule organizing centers (MTOCs). Centriole biogenesis and MTOC function both require the microtubule nucleator {gamma}-tubulin ring complex ({gamma}TuRC). The widely accepted view is that {gamma}TuRC localizes to the pericentriolar material (PCM), where it nucleates microtubules. {gamma}TuRC has also been observed at centriolar regions that lack PCM, but the significance of these findings is unclear. Here we have used expansion microscopy to map spatially and functionally distinct sub-populations of centrosomal {gamma}TuRC including in the centriole lumen. Luminal localization is mediated by augmin and both complexes are linked to the centriole inner scaffold through POC5. Disruption of luminal localization impairs centriole stability and cilia assembly, defects that are also observed in {gamma}TuRC mutant fibroblasts derived from a patient suffering from microcephaly with chorioretinopathy. These results identify a novel, non-canonical role of augmin-{gamma}TuRC in the centriole lumen that is linked to human disease.

cell biology↗

bioRxiv2020

Disruption of augmin-mediated microtubule nucleation in neural stem cells causes p53-dependent apoptosis and aborts brain development.

Microtubules that assemble the mitotic spindle are generated by three different mechanisms: centrosomal nucleation, chromatin-mediated nucleation, and nucleation from the surface of other microtubules mediated by the augmin complex. Impairment of centrosomal nucleation in apical progenitors of the developing mouse brain induces p53-dependent apoptosis and causes non-lethal microcephaly. Whether disruption of non-centrosomal nucleation has similar effects is unclear. Here we show, using mouse embryos, that conditional knockout of the augmin subunit Haus6 in apical progenitors led to spindle defects and mitotic delay. This triggered massive apoptosis and complete abortion of brain development. Co-deletion of p53 rescued cell death, but brain development was still aborted. This could be explained by exacerbated mitotic errors and resulting chromosomal defects including increased DNA damage. Surviving progenitors had lost apico-basal polarity and failed to organize a pseudostratified epithelium. Thus, in contrast to the centrosomal nucleation pathway, augmin is crucial for apical progenitor mitosis, and, even in the absence of p53, for progression of brain development.

cell biology↗