Regulation of postsynaptic RapGAP SPAR by Polo-like kinase 2 and the SCFbeta-TRCP ubiquitin ligase in hippocampal neurons.
Regulation of postsynaptic RapGAP SPAR by Polo-like kinase 2 and the SCFbeta-TRCP ubiquitin ligase in hippocampal neurons.
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DOI：
10.1074/jbc.m802475200
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发表时间：
2008-10-24
期刊：
影响因子：
--
通讯作者：
Harper JW
中科院分区：
文献类型：
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作者：
Ang XL;Seeburg DP;Sheng M;Harper JW
泛素-蛋白酶体通路（UPP）调节突触功能，但对哺乳动物突触中UPP的特异性靶点和机制知之甚少。我们在这里报告SCFβ-TRCP复合物，一种多亚基E3泛素连接酶，靶向突触后脊髓相关的Rap GT3激活蛋白（SPAR）在神经元中降解。SCFβ-TRCP对SPAR的降解依赖于活性诱导型蛋白激酶Polo样激酶2（Plk 2）。在Plk 2存在下，SPAR通过典型的磷酸降解决定子与SCFβ-TRCP复合物物理结合。在海马神经元中，通过过表达显性干扰β-TRCP或Cul 1构建体破坏SCFβ-TRCP复合物可阻止SPAR的Plk 2依赖性降解。 我们的结果确定了一种特异性E3遍在蛋白连接酶，该酶介导突触形态和功能的关键突触后调节因子的降解。
The ubiquitin-proteasome pathway (UPP) regulates synaptic function, but little is known about specific UPP targets and mechanisms in mammalian synapses. We report here that the SCFβ-TRCP complex, a multisubunit E3 ubiquitin ligase, targets the postsynaptic spine-associated Rap GTPase activating protein (SPAR) for degradation in neurons. SPAR degradation by SCFβ-TRCP depended on the activity-inducible protein kinase Polo-like kinase 2 (Plk2). In the presence of Plk2, SPAR physically associated with the SCFβ-TRCP complex through a canonical phosphodegron. In hippocampal neurons, disruption of the SCFβ-TRCP complex by overexpression of dominant interfering β-TRCP or Cul1 constructs prevented Plk2-dependent degradation of SPAR. Our results identify a specific E3 ubiquitin ligase that mediates degradation of a key postsynaptic regulator of synaptic morphology and function.