IGF-1 activates a cilium-localized noncanonical Gβγ signaling pathway that regulates cell-cycle progression.
IGF-1 activates a cilium-localized noncanonical Gβγ signaling pathway that regulates cell-cycle progression.
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DOI：
10.1016/j.devcel.2013.07.014
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发表时间：
2013-08-26
影响因子：
11.8
通讯作者：
Sung CH
中科院分区：
文献类型：
--
作者：
Yeh C;Li A;Chuang JZ;Saito M;Cáceres A;Sung CH
初级纤毛经历细胞周期依赖的组装和拆卸。新出现的数据表明，睫状体吸收是S相重入的一个检查点，而磷酸化(T94)Tctex-1的激活耦合了这两个事件。然而，触发这些过程的环境线索和分子机制仍然未知。在这里，我们发现胰岛素样生长-1(IGF1)通过引起纤毛吸收来加速G1-S的进展。IGF-1的促有丝分裂信号主要通过成纤维细胞和上皮细胞纤毛上的IGF-1受体(IGF-1R)传递。在纤毛的底部，磷酸化的胰岛素样生长因子-1R激活了AGS3调节的Gβγ信号通路，随后将磷酸化的(T94)Tctex-1重新招募到过渡区。干扰皮质祖细胞中这一途径的任何组成部分都会诱导神经元过早分化，并以增殖为代价。这些数据表明，在皮质发生过程中，纤毛转导的非典型的胰岛素样生长因子-1R-Gβγ-磷酸(T94)Tctex-1信号通路通过调节纤毛吸收和G1长度促进神经前体细胞的增殖。
Primary cilia undergo cell cycle-dependent assembly and disassembly. Emerging data suggest that ciliary resorption is a checkpoint for S phase re-entry, and that the activation of phospho(T94)Tctex-1 couples these two events. However, the environmental cues and molecular mechanisms that trigger these processes remain unknown. Here, we show that insulin-like growth-1 (IGF-1) accelerates G1-S progression by causing cilia to resorb. The mitogenic signals of IGF-1 are predominantly transduced through IGF-1 receptor (IGF-1R) on the cilia of fibroblasts and epithelial cells. At the base of the cilium, phosphorylated IGF-1R activates an AGS3-regulated Gβγ signaling pathway that subsequently recruits phospho(T94)Tctex-1 to the transition zone. Perturbing any component of this pathway in cortical progenitors induces premature neuronal differentiation at the expense of proliferation. These data suggest that during corticogenesis, a cilium-transduced, non-canonical IGF-1R-Gβγ–phospho(T94)Tctex-1 signaling pathway promotes the proliferation of neural progenitors through modulation of ciliary resorption and G1 length.
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影响因子：
4.8
作者：
Ghosh, M;Peterson, YK;Smrcka, AV
通讯作者：
Smrcka, AV
影响因子：
16.2
作者：
Lehtinen MK;Zappaterra MW;Chen X;Yang YJ;Hill AD;Lun M;Maynard T;Gonzalez D;Kim S;Ye P;D'Ercole AJ;Wong ET;LaMantia AS;Walsh CA
通讯作者：
Walsh CA
影响因子：
4.8
作者：
Dalle, S;Ricketts, W;Olefsky, JM
通讯作者：
Olefsky, JM
DOI：
10.1136/mp.55.1.46
发表时间：
2002-02-01
期刊：
JOURNAL OF CLINICAL PATHOLOGY-MOLECULAR PATHOLOGY
影响因子：
--
作者：
Buckley, DA;Loughran, G;O'Connor, R
通讯作者：
O'Connor, R
影响因子：
11.8
作者：
Chuang, JZ;Yeh, TY;Sung, CH
通讯作者：
Sung, CH