Proteins of the CNR family are multiple receptors for reelin

Proteins of the CNR family are multiple receptors for reelin
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DOI:
10.1016/s0092-8674(00)81552-4
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发表时间:
1999-12-10
期刊:
影响因子:
64.5
通讯作者:
Yagi, T
Yagi, T
中科院分区:
生物学1区
文献类型:
--
作者:
Senzaki, K;Ogawa, M;Yagi, T

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神经元的分层和定位需要Reelin和Src家族相关的哺乳动物Disabled(mDab 1)。钙粘蛋白相关神经元受体(CNR)基因在皮质层的神经元中表达,但在表达Reelin的Cajal-Retzius细胞中不表达。这使我们假设结合到Src家族的Fyn的CNR是Reelin的受体。在此,我们证实了CNR蛋白与Reelin的关联和共定位。这种结合被针对Reelin的CR-50抗体以及针对CNR产生的单克隆抗体阻断。两者都干扰了从Reelin到mDab 1的信号通路和体外皮层神经元的定位。这些结果强烈表明CNR家族蛋白是多种Reelin受体。此外,陆生脊椎动物之间的Reelin结合域的差异保护可能与大脑的多样性或复杂性有关。
Layering and positioning of neurons require Reelin-and Src family-associated mammalian Disabled (mDab1). Cadherin-related neuronal receptor (CNR) genes are expressed in neurons of the cortical layer, but not in Cajal-Retzius cells expressing Reelin. This leads us to hypothesize that CNRs bound to Fyn of the Src family are receptors for Reelin. Herein we confirm the association and colocalization of CNR proteins with Reelin. This binding is blocked by CR-50 antibody against Reelin, as well as by monoclonal antibodies produced against CNRs. Both disturb the signaling pathway from Reelin to mDab1 and the positioning of cortical neurons in vitro. These results strongly suggest that the CNR family proteins are multiple Reelin receptors. In addition, differential conservation of the Reelin-binding domain among terrestrial vertebrates may be pertinent to the diversity or complexity of brains.