Recruitment of scribble to the synaptic scaffolding complex requires GUK-holder, a novel DLG binding protein
Recruitment of scribble to the synaptic scaffolding complex requires GUK-holder, a novel DLG binding protein
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DOI：
10.1016/s0960-9822(02)00758-3
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发表时间：
2002-04-02
期刊：
影响因子：
9.2
通讯作者：
Budnik, V
中科院分区：
文献类型：
--
作者：
Mathew, D;Gramates, LS;Budnik, V
背景资料：膜相关鸟苷酸激酶（MAGUKs），如椎间盘-大（DLG），通过调节突触多蛋白复合物的组装在突触成熟中发挥关键作用。先前的研究已经揭示了DLG和另一种PDZ支架蛋白SCRIBBLE（SCRIB）之间的遗传相互作用，在发育上皮细胞中建立细胞极性的过程中。DLG和SCRIB在突触连接处可能的相互作用尚未得到解决。同样，这种相互作用的生物化学性质仍然难以捉摸，提出了关于这两种蛋白质的行动是coordinated.Results的机制的问题：在这里，我们报告了一个新的DLG相互作用的蛋白质，GUK-持有人，与GUK域的DLG相互作用，并动态表达在突触的布顿出芽分离。我们还表明，在果蝇突触DLG与SCRIB共定位，这种共定位可能是介导的GUKH和PDZ 2结构域的SCRIB之间的直接相互作用。我们发现，DLG，GUKH和SCRIB形成一个三方复杂的突触，其中DLG和GUKH是所需的适当的突触定位SCRIB.Conclusions：我们的研究结果提供了一种机制，通过该机制，发育重要的PDZ介导的复合物在突触相关联。
Background: Membrane-associated guanylate kinases (MAGUKs), such as Discs-Large (DLG), play critical roles in synapse maturation by regulating the assembly of synaptic multiprotein complexes. Previous studies have revealed a genetic interaction between DLG and another PDZ scaffolding protein, SCRIBBLE (SCRIB), during the establishment of cell polarity in developing epithelia. A possible interaction between DLG and SCRIB at synaptic junctions has not yet been addressed. Likewise, the biochemical nature of this interaction remains elusive, raising questions regarding the mechanisms by which the actions of both proteins are coordinated.Results: Here we report the isolation of a new DLG-interacting protein, GUK-holder, that interacts with the GUK domain of DLG and which is dynamically expressed during synaptic bouton budding. We also show that at Drosophila synapses DLG colocalizes with SCRIB and that this colocalization is likely to be mediated by direct interactions between GUKH and the PDZ2 domain of SCRIB. We show that DLG, GUKH, and SCRIB form a tripartite complex at synapses, in which DLG and GUKH are required for the proper synaptic localization of SCRIB.Conclusions: Our results provide a mechanism by which developmentally important PDZ-mediated complexes are associated at the synapse.