Recruitment of scribble to the synaptic scaffolding complex requires GUK-holder, a novel DLG binding protein

被引:109
作者
Mathew, D
Gramates, LS
Packard, M
Thomas, U
Bilder, D
Perrimon, N
Gorczyca, M
Budnik, V [1 ]
机构
[1] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA
[2] Univ Massachusetts, Mol & Cellular Biol Program, Amherst, MA 01003 USA
[3] Leibniz Inst Neurobiol, Dept Neurochem, D-39118 Magdeburg, Germany
[4] Harvard Univ, Sch Med, Dept Genet, HHMI, Boston, MA 02115 USA
关键词
D O I
10.1016/S0960-9822(02)00758-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:531 / 539
页数:9
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