2026-06-14T10:37:37Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
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
funder
Unión Europea. Comisión Europea
funder
Ministerio de Ciencia e Innovación (España)
funder
Comunidad de Madrid (España)
funder
Ministerio de Economía y Competitividad (España)
funder
Fundación ProCNIC
2019-07-29T06:41:49Z
2019-07-29T06:41:49Z
2016-11-17
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
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.
eng
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
journal article
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CalcineurinVariantCnAbeta1Controls_2016.pdf
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CalcineurinVariantCnAbeta1Controls_2016.pdf.txt