亲代谢型谷氨酸受体I组（mGluRI）和Trk受体激活对神经营养因子的调节性分泌是通过磷脂酶C信号通路介导的。
Regulated secretion of neurotrophins by metabotropic glutamate group I (mGluRI) and Trk receptor activation is mediated via phospholipase C signalling pathways.
作者信息
Canossa M, Gärtner A, Campana G, Inagaki N, Thoenen H
机构信息
Department of Neurobiochemistry, Max-Planck Institute of Neurobiology, Am Klopferspitz 18A, D-82152 Martinsried, Germany.
出版信息
EMBO J. 2001 Apr 2;20(7):1640-50. doi: 10.1093/emboj/20.7.1640.
Neurotrophins (NTs) play an essential role in modulating activity-dependent neuronal plasticity. In this context, the site and extent of NT secretion are of crucial importance. Here, we demonstrate that the activation of phospolipase C (PLC) and the subsequent mobilization of Ca(2+) from intracellular stores are essential for NT secretion initiated by both Trk and glutamate receptor activation. Mutational analysis of tyrosine residues, highly conserved in the cytoplasmic domain of all Trk receptors, revealed that the activation of PLC-gamma in cultured hippocampal neurons and nnr5 cells is necessary to mobilize Ca(2+) from intracellular stores, the key mechanism for regulated NT secretion. A similar signalling mechanism has been identified for glutamate-mediated NT secretion-which in part depends on the activation of PLC via metabotropic receptors-leading to the mobilization of Ca(2+) from internal stores by inositol trisphosphate. Thus, PLC-mediated signal transduction pathways are the common mechanisms for both Trk- and mGluRI-mediated NT secretion.
神经营养因子（NTs）在调节依赖活动的神经元可塑性方面发挥着重要作用。在这种情况下，NTs分泌的部位和程度至关重要。在此，我们证明磷脂酶C（PLC）的激活以及随后细胞内储存的Ca(2+)的动员对于由Trk和谷氨酸受体激活引发的NTs分泌至关重要。对所有Trk受体胞质结构域中高度保守的酪氨酸残基进行突变分析表明，培养的海马神经元和nnr5细胞中PLC-γ的激活对于从细胞内储存中动员Ca(2+)是必要的，这是调节NTs分泌的关键机制。已确定谷氨酸介导的NTs分泌存在类似的信号传导机制——这部分依赖于通过代谢型受体激活PLC——导致肌醇三磷酸从内部储存中动员Ca(2+)。因此，PLC介导的信号转导途径是Trk和mGluRI介导的NTs分泌的共同机制。
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