Kindlin-2 regulates mesenchymal stem cell differentiation through control of YAP1/TAZ.

The Journal of Cell Biology
Ling GuoChuanyue Wu

Abstract

Precise control of mesenchymal stem cell (MSC) differentiation is critical for tissue development and regeneration. We show here that kindlin-2 is a key determinant of MSC fate decision. Depletion of kindlin-2 in MSCs is sufficient to induce adipogenesis and inhibit osteogenesis in vitro and in vivo. Mechanistically, kindlin-2 regulates MSC differentiation through controlling YAP1/TAZ at both the transcript and protein levels. Kindlin-2 physically associates with myosin light-chain kinase in response to mechanical cues of cell microenvironment and intracellular signaling events and promotes myosin light-chain phosphorylation. Loss of kindlin-2 inhibits RhoA activation and reduces myosin light-chain phosphorylation, stress fiber formation, and focal adhesion assembly, resulting in increased Ser127 phosphorylation, nuclear exclusion, and ubiquitin ligase atrophin-1 interacting protein 4-mediated degradation of YAP1/TAZ. Our findings reveal a novel kindlin-2 signaling axis that senses the mechanical cues of cell microenvironment and controls MSC fate decision, and they suggest a new strategy to regulate MSC differentiation, tissue repair, and regeneration.

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Citations

Mar 22, 2018·Nature Reviews. Molecular Cell Biology·Kim Baumann
Jul 11, 2019·Current Protein & Peptide Science·Jie ZhangXi Ma
Jan 15, 2020·Bone Research·Huiling CaoGuozhi Xiao
Mar 28, 2020·Cell and Tissue Research·Abolfazl BarzegariGraciela Pavon-Djavid
Feb 21, 2019·Nature Communications·Ling GuoChuanyue Wu
May 28, 2019·Molecular & Cellular Oncology·Ling Guo, Chuanyue Wu
Mar 1, 2019·Scientific Reports·Ling GuoYaojiong Wu
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Boon C HengXuliang Deng
Oct 6, 2020·Frontiers in Bioengineering and Biotechnology·Koki YoshimotoKen-Ichiro Kamei
Oct 22, 2020·Bone Research·Yiming LeiGuozhi Xiao
Dec 29, 2020·Signal Transduction and Targeted Therapy·Xuekun FuGuozhi Xiao
Nov 13, 2020·Frontiers in Cell and Developmental Biology·Wenqing XieYusheng Li
Feb 19, 2021·ACS Biomaterials Science & Engineering·Kuan Un WongGiselle C Yeo
Jan 2, 2021·Bone Research·Huiling CaoGuozhi Xiao
Mar 16, 2021·Frontiers in Oncology·Heming GeHaiping Pei
Jun 13, 2021·Cell Death & Disease·Xiaochun ChiHongquan Zhang
Mar 25, 2021·American Journal of Respiratory Cell and Molecular Biology·Ping ZhangChuanyue Wu
Oct 23, 2020·Biochemistry·Justin RobertoPanayiotis O Vacratsis

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Methods Mentioned

BETA
flow cytometry
pulldown
pulldowns
coimmunoprecipitation
FRET
biosensor
pull-down
Assay
protein assay

Software Mentioned

CTAn
CellQuest
Elements F
EPSON Scan
NIS
GraphPad Prism
NRecon
ImageJ
FlowJo
Leica X

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