Homer: A protein that selectively binds metabotropic glutamate receptors
Homer: A protein that selectively binds metabotropic glutamate receptors
复制标题
DOI：
10.1038/386284a0
复制
发表时间：
1997-03-20
期刊：
影响因子：
64.8
通讯作者：
Worley, PF
中科院分区：
文献类型：
--
作者：
Brakeman, PR;Lanahan, AA;Worley, PF
膜蛋白的空间定位和聚集对神经元发育和突触可塑性至关重要。最近的研究发现，PDZ蛋白家族含有模块化的PDZ结构域，并与突触亲离子谷氨酸受体(1)和离子通道(2)相互作用。PDZ蛋白被认为在定义与其相互作用的蛋白质的细胞分布中起作用，在这里我们报道了一种新的树突状蛋白Hmer，它包含一个单一的PDZ样结构域，并特异性地结合到磷脂酰肌醇连接的代谢性谷氨酸受体的羧基末端。Homer与已知的PDZ蛋白高度不同，似乎代表了一个新的家族。荷马基因也不同于PDZ家族的成员，因为它的表达是作为一个即时早期基因调节的，并对生理突触活动做出动态反应，特别是在皮质发育期间。这种动态的转录控制表明，荷马介导了一种新的细胞机制，调节代谢性谷氨酸信号。
Spatial localization and clustering of membrane proteins is critical to neuronal development and synaptic plasticity. Recent studies have identified a family of proteins, the PDZ proteins, that contain modular PDZ domains and interact with synaptic ionotropic glutamate receptors(1) and ion channels(2). PDZ proteins are thought to have a role in defining the cellular distribution of the proteins that interact with them, Here we report a novel dendritic protein, Homer, that contains a single, PDZ-like domain and binds specifically to the carboxy terminus of phosphoinositide-linked metabotropic glutamate receptors. Homer is highly divergent from known PDZ proteins and seems to represent a novel family. The Homer gene is also distinct from members of the PDZ family in that its expression is regulated as an immediate early gene and is dynamically responsive to physiological synaptic activity, particularly during cortical development. This dynamic transcriptional control suggests that Homer mediates a novel cellular mechanism that regulates metabotropic glutamate signalling.