Rab8 attenuates Wnt signaling and is required for mesenchymal differentiation into adipocytes.
Rab8 attenuates Wnt signaling and is required for mesenchymal differentiation into adipocytes.
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DOI：
10.1016/j.jbc.2021.100488
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Gao N
中科院分区：
文献类型：
--
作者：
Stypulkowski E;Feng Q;Joseph I;Farrell V;Flores J;Yu S;Sakamori R;Sun J;Bandyopadhyay S;Das S;Dobrowolski R;Bonder EM;Chen MH;Gao N
间充质干细胞向脂肪细胞的分化需要外部刺激的协调，并依赖于初级纤毛的功能。Rab8小GTP酶是膜结合结构和信号传导货物的细胞内转运的调节剂。然而，由Rab8控制的内在运输网络对间充质组织分化的生理贡献尚未在体内和原代组织培养中完全确定。在这里，我们表明，缺乏Rab8的小鼠胚胎成纤维细胞（MEFs）在体内和体外脂肪细胞分化严重受损。Rab8a缺陷型、Rab8b缺陷型、Rab8a和Rab8b双缺陷型MEFs的免疫荧光定位和生化分析显示Rab8控制Lrp6囊泡区室、基底信号体的清除、卷曲两个受体的运输，从而在分化的MEFs中适当减弱Wnt信号。在诱导脂肪生成程序后，Rab8a和Rab8b缺陷的MEFs表现出严重缺陷的脂滴形成和异常纤毛形态，尽管总体上完整的纤毛生长和纤毛货物运输。我们的研究结果表明，细胞内Rab8交通调节诱导脂肪形成通过适当的定位Wnt受体的信号转导控制间充质细胞。
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.
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影响因子：
4.1
作者：
Cawthorn WP;Bree AJ;Yao Y;Du B;Hemati N;Martinez-Santibañez G;MacDougald OA
通讯作者：
MacDougald OA
影响因子：
56.9
作者：
Bilic, Josipa;Huang, Ya-Lin;Niehrs, Christof
通讯作者：
Niehrs, Christof
影响因子：
64.8
作者：
Davidson, G;Wu, W;Niehrs, C
通讯作者：
Niehrs, C
影响因子：
--
作者：
Hou, Rui;Jiang, Luo;Liu, Qifang
通讯作者：
Liu, Qifang
DOI：
10.1016/j.cub.2009.05.025
发表时间：
2009-07-14
期刊：
Current biology : CB
影响因子：
--
作者：
Berbari NF;O'Connor AK;Haycraft CJ;Yoder BK
通讯作者：
Yoder BK