Ripply2 recruits proteasome complex for Tbx6 degradation to define segment border during murine somitogenesis

ELife
Wei ZhaoYumiko Saga

Abstract

The metameric structure in vertebrates is based on the periodic formation of somites from the anterior end of the presomitic mesoderm (PSM). The segmentation boundary is defined by the Tbx6 expression domain, whose anterior limit is determined by Tbx6 protein destabilization via Ripply2. However, the molecular mechanism of this process is poorly understood. Here, we show that Ripply2 directly binds to Tbx6 in cultured cells without changing the stability of Tbx6, indicating an unknown mechanism for Tbx6 degradation in vivo. We succeeded in reproducing in vivo events using a mouse ES induction system, in which Tbx6 degradation occurred via Ripply2. Mass spectrometry analysis of the PSM-fated ES cells revealed that proteasomes are major components of the Ripply2-binding complex, suggesting that recruitment of a protein-degradation-complex is a pivotal function of Ripply2. Finally, we identified a motif in the T-box, which is required for Tbx6 degradation independent of binding with Ripply2 in vivo.

References

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Citations

Mar 27, 2020·American Journal of Medical Genetics. Part a·Margaux Serey-GautLionel Van Maldergem

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Methods Mentioned

BETA
immunoprecipitation
pull-down
pull down
ubiquitination
Co-immunoprecipitation
transgenic
co-immunoprecipitation assay
Assay
transfection
PCR

Software Mentioned

ImageJ

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