Biology subjects

Failli, M.

Publications and source records attributed to Failli, M..

2 recordsLinked to original sources

bioRxiv2020

β-catenin perturbations control differentiation programs in mouse embryonic stem cells

The Wnt/{beta}-catenin pathway is involved in development, cancer and embryonic stem cell (ESC) maintenance; its dual role in stem cell self-renewal and differentiation is still controversial. Here, by applying an in vitro system enabling inducible gene expression control, we report that moderate induction of transcriptionally active exogenous {beta}- catenin in {beta}-catenin null mouse ESCs promotes epiblast-like cell (EpiLC) derivation in vitro. Instead, in wild type cells moderate chemical pre-activation of the Wnt/{beta}-catenin pathway promotes EpiLC in vitro derivation. Finally, we suggest that moderate {beta}- catenin levels in {beta}-catenin null mouse ESCs favour early stem cell commitment towards mesoderm if the exogenous protein is induced only in the ground state of pluripotency condition, or endoderm if the induction is maintained during the differentiation. Overall, our results confirm previous findings about the role of {beta}-catenin in pluripotency and differentiation, while indicating a role for its doses in promoting specific differentiation programs.

cell biology↗

bioRxiv2019

The TRAPP complex mediates secretion arrest induced by stress granule assembly

The TRAnsport-Protein-Particle (TRAPP) complex controls multiple membrane trafficking steps and is thus strategically positioned to mediate cell adaptation to diverse environmental conditions, including acute stress. We have identified TRAPP as a key component of a branch of the integrated stress response that impinges on the early secretory pathway. TRAPP associates with and drives the recruitment of the COPII coat to stress granules (SGs) leading to vesiculation of the Golgi complex and an arrest of ER export. Interestingly, the relocation of TRAPP and COPII to SGs only occurs in actively proliferating cells and is CDK1/2-dependent. We show that CDK1/2 activity controls the COPII cycle at ER exit sites (ERES) and that its inhibition prevents TRAPP/COPII relocation to SGs by stabilizing them at the ERES. Importantly, TRAPP is not just a passive constituent of SGs but controls their maturation since SGs that assemble in TRAPP-depleted cells are smaller and are no longer able to recruit RACK1 and Raptor, rendering the cells more prone to undergo apoptosis upon stress exposure.

cell biology↗