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Abstract：
Adult Neural Stem Cells (aNSCs) in the ventricular-subventricular zone (V-SVZ) are largely quiescent. Here, we characterize the mechanism underlying the functional role of a cell-signalling inhibitory protein, LRIG1, in the control of aNSCs proliferation. Using Lrig1 knockout models, we show that Lrig1 ablation results in increased aNSCs proliferation with no change in neuronal progeny and that this hyperproliferation likely does not result solely from activation of the epidermal growth factor receptor (EGFR). Loss of LRIG1, however, also leads to impaired activation of transforming growth factor beta (TGFβ) and bone morphogenic protein (BMP) signalling. Biochemically, we show that LRIG1 binds TGFβ/BMP receptors and the TGFβ1 ligand. Finally, we show that the consequences of these interactions are to facilitate SMAD phosphorylation. Collectively, these data suggest that unlike in embryonic NSCs where EGFR may be the primary mechanism of action, in aNSCs, LRIG1 and TGFβ pathways function together to fulfill their inhibitory roles.
摘要：
心室-室下区（V-SVZ）中的成年神经干细胞（aNSC）在很大程度上是静止的。这里,我们描述了细胞信号传导抑制蛋白的功能作用的潜在机制，LRIG1，在控制aNSC增殖中。使用Lrig1敲除模型，我们表明,Lrig1消融导致aNSCs增殖增加,而神经元子代无变化,而且这种过度增殖可能并非仅由表皮生长因子受体(EGFR)的激活引起.然而，LRIG1的损失，还导致转化生长因子β(TGFβ)和骨形态发生蛋白(BMP)信号传导的活化受损。生物化学,我们显示LRIG1结合TGFβ/BMP受体和TGFβ1配体。最后,我们表明，这些相互作用的后果是促进SMAD磷酸化。总的来说，这些数据表明，与胚胎神经干细胞不同，EGFR可能是主要的作用机制，在ASCs中，LRIG1和TGFβ途径共同发挥作用以实现其抑制作用。
