Thrombospondin-1 binds to ApoER2 and VLDL receptor and functions in postnatal neuronal migration
Thrombospondin-1 binds to ApoER2 and VLDL receptor and functions in postnatal neuronal migration
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DOI：
10.1038/emboj.2008.223
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发表时间：
2008-11-19
期刊：
影响因子：
11.4
通讯作者：
Nimpf, Johannes
中科院分区：
文献类型：
--
作者：
Blake, Sophia M.;Strasser, Vera;Nimpf, Johannes
载脂蛋白E受体2（ApoER 2）、极低密度脂蛋白受体（VLDLR）和Dab 1是Reelin信号级联的主要组分。Reelin是迄今为止在通过该途径的信号传导中定义的唯一配体。出生后的神经元前体细胞从脑室下区（SVZ）迁移到嗅球（OB），然而，依赖于ApoER 2和Dab 1，但功能独立于Reelin。在这里，我们表明，血小板反应蛋白-1（THBS-1）是一种新的生理配体ApoER 2和VLDLR。THBS-1存在于SVZ和沿着整个吻端洄游流（RMS）。与ApoER 2和VLDLR结合并诱导Dab 1磷酸化。与Reelin相反，它不诱导Dab 1降解或Akt磷酸化，但稳定来自脑室下外植体的神经元前体链。THBS-1的缺乏导致RMS的解剖异常，并导致进入OB的出生后神经元前体减少。
Apolipoprotein E receptor 2 (ApoER2), very low-density lipoprotein receptor (VLDLR), and Dab1 are the main components of the Reelin signalling cascade. Reelin is the sole ligand defined so far in signalling through this pathway. Postnatal migration of neuronal precursors from the subventricular zone (SVZ) to the olfactory bulb (OB), however, depends on ApoER2 and Dab1, but functions independently of Reelin. Here, we show that thrombospondin-1 (THBS-1) is a novel physiological ligand for ApoER2 and VLDLR. THBS-1 is present in the SVZ and along the entire rostral migratory stream (RMS). It binds to ApoER2 and VLDLR and induces phosphorylation of Dab1. In contrast to Reelin, it does not induce Dab1 degradation or Akt phosphorylation, but stabilizes neuronal precursor chains derived from subventricular explants. Lack of THBS-1 results in anatomical abnormalities of the RMS and leads to a reduction of postnatal neuronal precursors entering the OB.