Loss of Memo, a novel FGFR regulator, results in reduced lifespan
Loss of Memo, a novel FGFR regulator, results in reduced lifespan
复制标题
DOI：
10.1096/fj.13-228320
复制
发表时间：
2014-01-01
期刊：
影响因子：
4.8
通讯作者：
Hynes, Nancy E.
中科院分区：
文献类型：
--
作者：
Haenzi, Barbara;Bonny, Olivier;Hynes, Nancy E.
Memo 是一种广泛表达的 33 kDa 蛋白，是调蛋白 (HRG)、表皮生长因子 (EGF) 和成纤维细胞生长因子 (FGF) 诱导的细胞运动所需的。对野生型或 Memo 敲除小鼠胚胎成纤维细胞进行研究，以进一步研究 Memo 在 FGFR 下游的作用。我们证明 Memo 与 FGFR 信号体相关，并且对于信号传导的最佳激活是必需的。为了揭示 Memo 的生理作用，我们培育了 Memo 条件敲除小鼠。这些动物表现出寿命缩短、胰岛素敏感性增加、身材矮小、头发变白、脱发、脊柱后凸、皮下脂肪减少以及附睾精子减少。与表达 Memo 的对照同窝小鼠相比，Memo 敲除小鼠的活性维生素 D、1,25-二羟基维生素 D-3 (1,25(OH)(2)D) 和钙的血清水平也有所升高。总之，体内和体外模型的结果支持这样的假设：Memo 是 FGFR 信号传导的新型调节剂，在控制 1,25(OH)(2)D 产生和正常钙稳态中发挥作用。Haenzi, B.、Bonny, O.、Masson, R.、Lienhard, S.、Dey, J. H.、Kuro-o, M.、Hynes, N. E. Memo 的丢失，一种新型 FGFR 调节剂，导致寿命缩短。
Memo is a widely expressed 33-kDa protein required for heregulin (HRG)-, epidermal growth factor (EGF)-, and fibroblast growth factor (FGF)-induced cell motility. Studies in mouse embryonic fibroblasts, wild-type or knockout for Memo, were performed to further investigate the role of Memo downstream of FGFR. We demonstrated that Memo associates with the FGFR signalosome and is necessary for optimal activation of signaling. To uncover Memo's physiological role, Memo conditional-knockout mice were generated. These animals showed a reduced life span, increased insulin sensitivity, small stature, graying hair, alopecia, kyphosis, loss of subcutaneous fat, and loss of spermatozoa in the epididymis. Memo-knockout mice also have elevated serum levels of active vitamin D, 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D), and calcium compared to control littermates expressing Memo. In summary, the results from in vivo and in vitro models support the hypothesis that Memo is a novel regulator of FGFR signaling with a role in controlling 1,25(OH)(2)D production and normal calcium homeostasis.Haenzi, B., Bonny, O., Masson, R., Lienhard, S., Dey, J. H., Kuro-o, M., Hynes, N. E. Loss of Memo, a novel FGFR regulator, results in reduced lifespan.