Regulation of postsynaptic structure and protein localization by the Rho-type guanine nucleotide exchange factor dPix

Regulation of postsynaptic structure and protein localization by the Rho-type guanine nucleotide exchange factor dPix
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DOI:
10.1016/s0896-6273(01)00485-8
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发表时间:
2001-11-08
期刊:
影响因子:
16.2
通讯作者:
Goodman, CS
Goodman, CS
中科院分区:
医学1区
文献类型:
--
作者:
Parnas, D;Haghighi, AP;Goodman, CS

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dpix的突变是从果蝇中控制突触结构的基因的大规模筛选中恢复的。dpix编码dPix,一种与哺乳动物Pix同源的Rho型鸟嘌呤核苷酸交换因子(RtGEF)。在这里,我们表明,dPix起着重要的作用,在调节突触后结构和蛋白质定位在果蝇的神经muscular接头。dpix突变导致PDZ蛋白Dig、细胞粘附分子Fas II和谷氨酸受体亚基GluRIIA的突触水平降低,并导致丝氨酸/苏氨酸激酶Pak和突触下网状物的完全减少。这些突变突触的电生理几乎正常。许多,但不是全部,dpix缺陷介导通过dPak,Cdc 42/Rac 1激活激酶家族的成员。因此,Rho型GEF和Rho型效应激酶调节突触后结构。
Mutations in dpix were recovered from a large-scale screen in Drosophila for genes that control synaptic structure. dpix encodes dPix, a Rho-type guanine nucleotide exchange factor (RtGEF) homologous to mammalian Pix. Here we show that dPix plays a major role in regulating postsynaptic structure and protein localization at the Drosophila glutamatergic neuromuscular junction. dpix mutations lead to decreased synaptic levels of the PDZ protein Dig, the cell adhesion molecule Fas II, and the glutamate receptor subunit GluRIIA, and to a complete reduction of the serine/threonine kinase Pak and the subsynaptic reticulum. The electrophysiology of these mutant synapses is nearly normal. Many, but not all, dpix defects are mediated through dPak, a member of the family of Cdc42/Rac1-activated kinases. Thus, a Rho-type GEF and Rho-type effector kinase regulate postsynaptic structure.