ZNRF Proteins Constitute a Family of Presynaptic E3 Ubiquitin Ligases
ZNRF Proteins Constitute a Family of Presynaptic E3 Ubiquitin Ligases
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DOI：
10.1523/jneurosci.23-28-09385.2003
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发表时间：
2003-10
期刊：
影响因子：
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通讯作者：
T. Araki;J. Milbrandt
中科院分区：
文献类型：
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作者：
T. Araki;J. Milbrandt
蛋白质泛素化最近被认为与神经发育、可塑性和退化有关。我们之前鉴定了ZNRF1/nin283蛋白，该蛋白具有独特的，进化保守的c端结构域，包含并列的锌指/环指组合。在这里，我们描述了一个密切相关的蛋白ZNRF2的鉴定，从而定义了一个新的znrfe3泛素连接酶家族。ZNRF1和ZNRF2都具有E3泛素连接酶活性，并在神经系统中高度表达，特别是在发育过程中。在神经元中，znrrf蛋白位于突触前末端的不同隔室中：ZNRF1与突触囊泡膜相关，而ZNRF2存在于突触前质膜中。突变的ZNRF蛋白具有破坏的环指，这是其E3功能所必需的结构域，可以抑制PC12细胞中的Ca2+依赖性胞外分泌。这些数据表明，ZNRF蛋白通过其泛素连接酶活性在神经元传递和可塑性的建立和维持中发挥作用。
Protein ubiquitination has been implicated recently in neural development, plasticity, and degeneration. We previously identified ZNRF1/nin283, a protein with a unique, evolutionarily conserved C-terminal domain containing a juxtaposed zinc finger/RING finger combination. Here we describe the identification of a closely related protein, ZNRF2, thus defining a novel family of ZNRF E3 ubiquitin ligases. Both ZNRF1 and ZNRF2 have E3 ubiquitin ligase activity and are highly expressed in the nervous system, particularly during development. In neurons, ZNRF proteins are located in different compartments within the presynaptic terminal: ZNRF1 is associated with synaptic vesicle membranes, whereas ZNRF2 is present in presynaptic plasma membranes. Mutant ZNRF proteins with a disrupted RING finger, a domain necessary for their E3 function, can each inhibit Ca2+-dependent exocytosis in PC12 cells. These data suggest that ZNRF proteins play a role in the establishment and maintenance of neuronal transmission and plasticity via their ubiquitin ligase activity.