ZIP3, a new splice variant of the PKC-ζ-interacting protein family, binds to GABAc receptors, PKC-ζ, and Kvβ2
ZIP3, a new splice variant of the PKC-ζ-interacting protein family, binds to GABAc receptors, PKC-ζ, and Kvβ2
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DOI：
10.1074/jbc.m205162200
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发表时间：
2003-02-21
影响因子：
4.8
通讯作者：
Enz, R
中科院分区：
文献类型：
--
作者：
Croci, C;Brandstätter, JH;Enz, R
修饰酶对离子通道和神经递质受体的正确靶向是控制神经元兴奋性的重要生物学机制。最近克隆的蛋白激酶C-zeta相互作用蛋白（ZIP1, ZIP2）发现了连接非典型蛋白激酶PKC-zeta与靶蛋白的新支架。GABA(C)受体由三个p亚基（rho1-3）组成，它们在视网膜中高度表达，聚集在双极细胞的突触末端。对GABAc受体rho3亚基的酵母双杂交筛选鉴定出ZIP蛋白家族的一个新的c端剪接变体ZIP3。ZIP3在包括视网膜在内的非神经元组织和神经元组织中普遍表达。ZIP3的rho3结合区含有一个zz -锌指结构域，该结构域与rho1-3中保守的10个氨基酸相互作用，而在GABA(a)受体中不存在。一致地，只有rho1-3亚基与ZIP3结合。ZIP3与ZIP1-3形成二聚体，并与PKC-zeta和摇床型钾通道亚基Kvbeta2相互作用。ZIP3的不同结构域与PKC-zeta和rho3亚基相互作用，并在体外证明了ZIP3、PKC-zeta和rho3的同时组装。视网膜中ZIP3结合伙伴的亚细胞共表达支持了所提出的蛋白质相互作用。我们的研究结果表明形成了一个包含PKC-zeta ZIP3和GABA(C)受体的三元突触后复合体。
The correct targeting of modifying enzymes to ion channels and neurotransmitter receptors represents an important biological mechanism to control neuronal excitability. The recent cloning of protein kinase C-zeta interacting proteins (ZIP1, ZIP2) identified new scaffolds linking the atypical protein kinase PKC-zeta to target proteins. GABA(C) receptors are composed of three p subunits (rho1-3) that are highly expressed in the retina, where they are clustered at synaptic terminals of bipolar cells. A yeast two-hybrid screen for the GABAc receptor rho3 subunit identified ZIP3, a new C-terminal splice variant of the ZIP protein family. ZIP3 was ubiquitously expressed in non-neuronal and neuronal tissues, including the retina. The rho3-binding region of ZIP3 contained a ZZ-zinc finger domain, which interacted with 10 amino acids conserved in rho1-3 but not in GABA(A) receptors. Consistently, only rho1-3 subunits bound to ZIP3. ZIP3 formed dimers with ZIP1-3 and interacted with PKC-zeta and the shaker-type potassium channel subunit Kvbeta2. Different domains of ZIP3 interacted with PKC-zeta and the rho3 subunit, and simultaneous assembly of ZIP3, PKC-zeta and rho3 was demonstrated in vitro. Subcellular co-expression of ZIP3 binding partners in the retina supported the proposed protein interactions. Our results indicate the formation of a ternary postsynaptic complex containing PKC-zeta ZIP3, and GABA(C) receptors.