Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1

Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1
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DOI:
10.1016/s0896-6273(00)80689-3
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发表时间:
1999-01-01
期刊:
影响因子:
16.2
通讯作者:
Huganir, RL
Huganir, RL
中科院分区:
医学1区
文献类型:
--
作者:
Xia, J;Zhang, XQ;Huganir, RL

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神经递质受体的突触聚集对于神经元中有效的信号转导和整合至关重要。含有PDZ结构域的蛋白质,如PSD-95/SAP90,与多种受体的细胞内C末端相互作用,被认为在受体与特定突触的靶向和锚定中起重要作用。在这里,我们证明了PICK1(与C激酶相互作用的蛋白),一个含有PDZ结构域的蛋白,在体外和体内与alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic酸(AMPA)受体的C末端相互作用。在神经元中,PICK1与AMPA受体共同定位于兴奋性突触。此外,PICK1在异源表达系统中诱导AMPA受体聚集。这些结果提示,PICK1可能通过调节AMPA受体的突触靶向,在突触传递的调节中发挥重要作用。
Synaptic clustering of neurotransmitter receptors is crucial for efficient signal transduction and integration in neurons. PDZ domain-containing proteins such as PSD-95/SAP90 interact with the intracellular C termini of a variety of receptors and are thought to be important in the targeting and anchoring of receptors to specific synapses. Here, we show that PICK1 (protein interacting with C kinase), a PDZ domain-containing protein, interacts with the C termini of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptors in vitro and in vivo. In neurons, PICK1 specifically colocalizes with AMPA receptors at excitatory synapses. Furthermore, PICK1 induces clustering of AMPA receptors in heterologous expression systems. These results suggest that PICK1 may play an important role in the modulation of synaptic transmission by regulating the synaptic targeting of AMPA receptors.