FADD phosphorylation impaired islet morphology and function
FADD phosphorylation impaired islet morphology and function
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DOI：
10.1002/jcp.24885
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发表时间：
2015-07
影响因子：
5.6
通讯作者：
Chun Yao;Hongqin Zhuang;Wei Cheng;Yan Lin;Pan Du;Bingya Yang;Xiaofeng Huang;Sheng Chen;Q. Hu;Z. Hua
中科院分区：
文献类型：
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作者：
Chun Yao;Hongqin Zhuang;Wei Cheng;Yan Lin;Pan Du;Bingya Yang;Xiaofeng Huang;Sheng Chen;Q. Hu;Z. Hua
先前的研究表明，Fas - FasL通路及其下游caspase - 8可以调节胰岛质量和胰岛素分泌。Fas相关死亡结构域蛋白（Fas - death domain containing protein， FADD）作为Fas - FasL信号传导的经典接头，通过其磷酸化参与许多非凋亡过程。然而，其在胰岛中的作用至今尚未得到评价。通过对FADD磷酸化（FADD - D）和野生型（WT） mef的比较蛋白质组学和生物信息学分析，我们发现FADD磷酸化导致三种参与胰岛分化和功能的蛋白失调。为了解决这一问题，我们进一步分析了FADD‐D小鼠模型，该模型模拟了FADD在小鼠中的组成性磷酸化表达。我们通过胰岛的免疫组织学分析证实了蛋白质组学结果。此外，我们发现FADD‐D小鼠胰岛面积减少，FADD‐D胰岛葡萄糖刺激胰岛素分泌（GSIS）受损。这些数据提示FADD在胰岛发育和胰岛素分泌中的新作用。j .细胞。中国生物医学工程学报，2016,31(2):448 - 456。©2015 Wiley Periodicals, Inc., A Wiley Company
Previous studies have indicated that Fas‐FasL pathway and its downstream caspase‐8 can regulate islet mass and insulin secretion. As a classical adaptor in Fas‐FasL signaling, Fas‐associated death domain‐containing protein (FADD) takes part in many non‐apoptosis processes regulated by its phosphorylation. However, its role in islets has not been evaluated to date. Here, through comparative proteomics and bioinformatic analysis on FADD phosphorylated (FADD‐D) and wild‐type (WT) MEFs, we found three proteins involved in islet differentiation and function were dysregulated due to FADD phosphorylation. The mouse model of FADD‐D, which mimics constitutive phosphorylated FADD expression in mice, was further analyzed to address this issue. We confirmed the proteomic results by immunohistological analyses on pancreatic islets. In addition, we found that FADD‐D mice displayed decreased islet area, and the glucose stimulated insulin secretion (GSIS) of FADD‐D islets was impaired. These data suggest a novel role of FADD in islet development and insulin secretion. J. Cell. Physiol. 230: 1448–1456, 2015. © 2015 Wiley Periodicals, Inc., A Wiley Company