Synaptic localization of membrane-associated guanylate kinase-interacting protein mediated by the pleckstrin homology domain
Synaptic localization of membrane-associated guanylate kinase-interacting protein mediated by the pleckstrin homology domain
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DOI：
10.1046/j.1460-9568.2002.01987.x
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发表时间：
2002-05-01
影响因子：
3.4
通讯作者：
Hata, Y
中科院分区：
文献类型：
--
作者：
Iida, J;Nishimura, W;Hata, Y
膜相关鸟苷激酶相互作用蛋白（MAGUIN）是一种结合突触后密度(PSD)-95和突触支架分子（S-SCAM）的蛋白。MAGUIN具有1个不育α基序、1个ksr （Cnk）连接器增强子（CRIC）保守区、1个PSD-95/Dlg-A/ZO-1 （PDZ）和1个pleckstrin同源结构域（PH）。有两种异构体，magun -1和-2。magun -1通过c端结合PSD-95和S-SCAM的PDZ结构域，而magun -2不结合PSD-95或S-SCAM。在这里，我们已经确定magin -2也定位于突触，并且magin的突触定位依赖于pleckstrin同源结构域。过表达的c端pdz结合区抑制PSD-95的突触靶向性。此外，MAGUIN的突触靶向不需要n -甲基-d-天冬氨酸（NMDA）受体活性。这些发现表明，magin -1和-2通过PH结构域被募集到突触中，随后magin -1在突触中与PSD-95相互作用。
Membrane-associated guanylate kinase-interacting protein (MAGUIN) has been identified as a protein binding postsynaptic density (PSD)-95 and synaptic scaffolding molecule (S-SCAM). MAGUIN has one sterile alpha motif, one conserved region in connector enhancer of ksr (Cnk) (CRIC), one PSD-95/Dlg-A/ZO-1 (PDZ) and one pleckstrin homology (PH) domain. There are two isoforms, MAGUIN-1 and -2. MAGUIN-1 binds the PDZ domains of PSD-95 and S-SCAM by the C-terminus, whereas MAGUIN-2 does not bind to PSD-95 or S-SCAM. Here, we have determined that MAGUIN-2 is also localized at synapses and that the synaptic localization of MAGUIN depends on the pleckstrin homology domain. The overexpressed C-terminal PDZ-binding region inhibits the synaptic targeting of PSD-95. Furthermore, the synaptic targeting of MAGUIN does not require N-methyl-d-aspartate (NMDA) receptor activity. These findings suggest that MAGUIN-1 and -2 are recruited to synapses by the PH domain and that MAGUIN-1 subsequently interacts with PSD-95 at synapses.