TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression
Name
s41467-019-08287-x.pdf
Description
Published version
Size
1.49 MB
Format
Unknown
Checksum (MD5)
93b4ed6ec7b2f3a95b1fc1f9f2cd3030
Author(s)
Hwang, Jun-Ha
Kim, A Rum
Kim, Kyung Min
Il Park, Jung
Oh, Ho Taek
Moon, Sung A
Byun, Mi Ran
Jeong, Hana
Kim, Hyo Kyung
Yaffe, Michael B
Date Issued
2019
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Version
Final published version
Abstract
© 2019, The Author(s). Insulin regulates blood glucose levels by binding its receptor and stimulating downstream proteins through the insulin receptor substrate (IRS). Impaired insulin signalling leads to metabolic syndrome, but the regulation of this process is not well understood. Here, we describe a novel insulin signalling regulatory pathway involving TAZ. TAZ upregulates IRS1 and stimulates Akt- and Glut4-mediated glucose uptake in muscle cells. Muscle-specific TAZ-knockout mice shows significantly decreased Irs1 expression and insulin sensitivity. Furthermore, TAZ is required for Wnt signalling-induced Irs1 expression, as observed by decreased Irs1 expression and insulin sensitivity in muscle-specific APC- and TAZ-double-knockout mice. TAZ physically interacts with c-Jun and Tead4 to induce Irs1 transcription. Finally, statin administration decreases TAZ, IRS1 level and insulin sensitivity. However, in myoblasts, the statin-mediated decrease in insulin sensitivity is counteracted by the expression of a constitutively active TAZ mutant. These results suggest that TAZ is a novel insulin signalling activator that increases insulin sensitivity and couples Hippo/Wnt signalling and insulin sensitivity.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/S41467-019-08287-X
