Dataset Information

Muscle stems cell LC-MS - Common and Distinctive Functions of the Hippo Effectors Taz and Yap in Skeletal Muscle Stem Cell Function

ABSTRACT: Abstract Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via interaction with Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed Taz in vivo and ex vivo in comparison to Yap. Taz was expressed in activated satellite cells. siRNA knockdown or constitutive expression of wildtype or constitutively active TAZ mutants showed that TAZ promoted proliferation, a function that was shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation. Functionally, while muscle growth was mildly affected in Taz (gene symbol Wwtr1-/-) knockout mice, there were no overt effect on regeneration. However, conditional knockout of Yap in satellite cells of Pax7Cre-ERT2/+ : Yapflox/flox : Rosa26Lacz mice produced a marked regeneration deficit. To identify potential mechanisms, microarray analysis showed many common Taz/Yap targets, but Taz also regulates some genes independently of Yap, including myogenic genes such as Pax7, Myf5 and Myod1. Proteomic analysis of Yap/Taz revealed many common binding partners, but Taz also interacts with proteins distinct from Yap, that are mainly involved in myogenesis and aspects of cytoskeleton organization. Neither TAZ nor YAP bind members of the Wnt destruction complex but both extensively changed expression of Wnt and Wnt-cross talking genes with known roles in myogenesis. Finally, TAZ operates through Tead4 to enhance myogenic differentiation. In summary, Taz and Yap have overlapping functions in promoting myoblast proliferation but Taz then switches to promote myogenic differentiation.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Myoblast

SUBMITTER: David Matallanas

LAB HEAD: David Matallanas

PROVIDER: PXD005751 | Pride | 2017-06-13

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20150821_difer_TA2_1.raw	Raw
	20150821_difer_TA2_1_150823082254.raw	Raw
	20150821_difer_TA2_2.raw	Raw
	20150821_difer_TA2_2_150823093329.raw	Raw
	20150821_difer_TA2_3.raw	Raw

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Publications

Common and Distinctive Functions of the Hippo Effectors Taz and Yap in Skeletal Muscle Stem Cell Function.

Sun Congshan C De Mello Vanessa V Mohamed Abdalla A Ortuste Quiroga Huascar P HP Garcia-Munoz Amaya A Al Bloshi Abdullah A Tremblay Annie M AM von Kriegsheim Alexander A Collie-Duguid Elaina E Vargesson Neil N Matallanas David D Wackerhage Henning H Zammit Peter S PS

Stem cells (Dayton, Ohio) 20170627 8

Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analyzed Taz in vivo and ex vivo in comparison with Yap. Small interfering RNA knockdown or retroviral-mediated expression of wild-type human or constitutively active TAZ mutants in satellite cells showed that TAZ promoted proliferation, a function shared with YAP. Ho ...[more]

PMID: 28589555

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