Imperial College London
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DrPaulBarton

Faculty of Medicine, National Heart & Lung Institute

Honorary Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7351 8140p.barton Website

 
 
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Location

 

2054Sydney StreetRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gómez-Salinero:2016:10.1016/j.chembiol.2016.09.010,
author = {Gómez-Salinero, JM and López-Olañeta, MM and Ortiz-Sánchez, P and Larrasa-Alonso, J and Gatto, A and Felkin, LE and Barton, PJ and Navarro-Lérida, I and Ángel, Del Pozo M and García-Pavía, P and Sundararaman, B and Giovinazo, G and Yeo, GW and Lara-Pezzi, E},
doi = {10.1016/j.chembiol.2016.09.010},
journal = {Cell Chemical Biology},
pages = {1372--1382},
title = {The Calcineurin Variant CnAβ1 controls mouse embryonic stem cell differentiation by directing mTORC2 membrane localization and activation},
url = {http://dx.doi.org/10.1016/j.chembiol.2016.09.010},
volume = {23},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Gómez-Salinero,JM
AU  - López-Olañeta,MM
AU  - Ortiz-Sánchez,P
AU  - Larrasa-Alonso,J
AU  - Gatto,A
AU  - Felkin,LE
AU  - Barton,PJ
AU  - Navarro-Lérida,I
AU  - Ángel,Del Pozo M
AU  - García-Pavía,P
AU  - Sundararaman,B
AU  - Giovinazo,G
AU  - Yeo,GW
AU  - Lara-Pezzi,E
DO  - 10.1016/j.chembiol.2016.09.010
EP  - 1382
PY  - 2016///
SN  - 2451-9456
SP  - 1372
TI  - The Calcineurin Variant CnAβ1 controls mouse embryonic stem cell differentiation by directing mTORC2 membrane localization and activation
T2  - Cell Chemical Biology
UR  - http://dx.doi.org/10.1016/j.chembiol.2016.09.010
UR  - http://hdl.handle.net/10044/1/41915
VL  - 23
ER  -
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