Rab8 attenuates Wnt signaling and is required for mesenchymal differentiation into adipocytes

Autor: Soumyashree Das, Edward M. Bonder, Ivor Joseph, Miao-Hsueh Chen, Jiaxin Sun, Victoria Farrell, Nan Gao, Radek Dobrowolski, Qiang Feng, Ewa Stypulkowski, Juan Flores, Ryotaro Sakamori, Shiyan Yu, Sheila Bandyopadhyay
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Frizzled
adipocyte
Biochemistry
03 medical and health sciences
Wnt
Mice
primary cilia
FBS
fetal bovine serum
Intraflagellar transport
Rab8
Adipocytes
Animals
Cilia
frizzled
Molecular Biology
Wnt Signaling Pathway
PPAR-γ
peroxisome proliferator-activated receptor γ
Cells
Cultured
KD
knockdown
Mice
Knockout
MEF
Adipogenesis
030102 biochemistry & molecular biology
Smo
Smoothened
Chemistry
Mesenchymal stem cell
Wnt signaling pathway
LRP6
Cell Differentiation
Mesenchymal Stem Cells
Cell Biology
differentiation
Fibroblasts
Embryonic stem cell
MEF
mouse embryonic fibroblast
Cell biology
mouse embryonic fibroblast
030104 developmental biology
C/EBPs
CCAAT/enhancer binding proteins
rab GTP-Binding Proteins
Smoothened
IFT
intraflagellar transport
pLRP6
phosphorylated LRP6
Research Article
Zdroj: The Journal of Biological Chemistry
ISSN: 1083-351X
0021-9258
Popis: Differentiation of mesenchymal stem cells into adipocyte requires coordination of external stimuli and depends upon the functionality of the primary cilium. The Rab8 small GTPases are regulators of intracellular transport of membrane-bound structural and signaling cargo. However, the physiological contribution of the intrinsic trafficking network controlled by Rab8 to mesenchymal tissue differentiation has not been fully defined in vivo and in primary tissue cultures. Here, we show that mouse embryonic fibroblasts (MEFs) lacking Rab8 have severely impaired adipocyte differentiation in vivo and ex vivo. Immunofluorescent localization and biochemical analyses of Rab8a-deficient, Rab8b-deficient, and Rab8a and Rab8b double-deficient MEFs revealed that Rab8 controls the Lrp6 vesicular compartment, clearance of basal signalosome, traffic of frizzled two receptor, and thereby a proper attenuation of Wnt signaling in differentiating MEFs. Upon induction of adipogenesis program, Rab8a- and Rab8b-deficient MEFs exhibited severely defective lipid-droplet formation and abnormal cilia morphology, despite overall intact cilia growth and ciliary cargo transport. Our results suggest that intracellular Rab8 traffic regulates induction of adipogenesis via proper positioning of Wnt receptors for signaling control in mesenchymal cells.
Databáze: OpenAIRE
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