2026-06-14T03:29:59Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/79712024-09-27T09:36:57Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc Gomez-Salinero, Jesus M. author Lopez-Olaneta, Marina author Ortiz-Sanchez, Paula author Larrasa-Alonso, Javier author Gatto, Alberto author Felkin, Leanne E author Barton, Paul J R author Navarro-Lerida, Inmaculada author del Pozo, Miguel Angel author García-Pavía, Pablo author Sundararaman, Balaji author Giovinazzo, Giovanna author Yeo, Gene W author Lara-Pezzi, Enrique author 2016-11-17 Embryonic stem cells (ESC) have the potential to generate all the cell lineages that form the body. However, the molecular mechanisms underlying ESC differentiation and especially the role of alternative splicing in this process remain poorly understood. Here, we show that the alternative splicing regulator MBNL1 promotes generation of the atypical calcineurin Aβ variant CnAβ1 in mouse ESCs (mESC). CnAβ1 has a unique C-terminal domain that drives its localization mainly to the Golgi apparatus by interacting with Cog8. CnAβ1 regulates the intracellular localization and activation of the mTORC2 complex. CnAβ1 knockdown results in delocalization of mTORC2 from the membrane to the cytoplasm, inactivation of the AKT/GSK3β/β-catenin signaling pathway, and defective mesoderm specification. In summary, here we unveil the structural basis for the mechanism of action of CnAβ1 and its role in the differentiation of mESCs to the mesodermal lineage. Cell Chem Biol. 2016; 23(11):1372-1382 10.1016/j.chembiol.2016.09.010 2451-9448 24519456 Cell chemical biology 27746127 http://hdl.handle.net/20.500.12105/7971 Akt CnAβ1 Golgi apparatus Rictor calcineurin mTOR splicing stem cells The Calcineurin Variant CnAβ1 Controls Mouse Embryonic Stem Cell Differentiation by Directing mTORC2 Membrane Localization and Activation