SYNCRIP, a cytoplasmic counterpart of heterogeneous nuclear ribonucleoprotein R, interacts with ubiquitous synaptotagmin isoforms
SYNCRIP, a cytoplasmic counterpart of heterogeneous nuclear ribonucleoprotein R, interacts with ubiquitous synaptotagmin isoforms
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DOI：
10.1074/jbc.275.13.9823
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发表时间：
2000-03-31
影响因子：
4.8
通讯作者：
Mikoshiba, K
中科院分区：
文献类型：
--
作者：
Mizutani, A;Fukuda, M;Mikoshiba, K
突触结合蛋白（Synaptotagmins，Syts）是一个由12种亚型组成的膜蛋白大家族，根据其表达模式可分为神经元特异性亚型（I-V，X，XI）和普遍存在的亚型（VI-M）。Syt-I是一种神经元特异性和丰富的同种型，已被很好地表征并假定为胞吐Ca 2+传感器。然而，其他同种型的功能仍然不清楚。在这里，我们报告说，无处不在的异构体的突触结合蛋白，Syt-VII，Syt-VIII，和Syt-IX相互作用的细胞质RNA结合蛋白，SYNCRIP（突触结合蛋白，细胞质RNA相互作用蛋白），通过其C2B结构域。SYNCRIP蛋白最初存在于小鼠脑裂解液中的Syt-Ⅱ C2 AB结构域结合组分中，其cDNA克隆结果表明，该蛋白与最近鉴定的异质核核糖核蛋白R（hnRNP R）高度同源。SYNCRIP蛋白在小鼠的各种组织中普遍且恒定地表达，与hnRNP R平行，SYNCRIP确实优先结合RNA而不是多聚（A）RNA;然而，与hnRNP R的核定位相反，SYNCRIP主要分布在细胞质中，如通过生化分离和免疫组织化学研究所判断的。体外结合实验表明，SYNCRIP与Syts的C2B结构域（Syt-V、-VI和-X除外）具有潜在的相互作用。此外，SYNCRIP和Syt-VII，-VIII，或-IX之间的相互作用，揭示了使用COS细胞瞬时表达每个Syt亚型的免疫共沉淀实验，这些发现表明，SYNCRIP是无处不在的类型的Syts的目标，并暗示无处不在的Syts参与调节细胞质mRNA的动态。
Synaptotagmins (Syts) are a large family of membrane proteins consisted of at least 12 isoforms, They are categorized in neuron-specific isoforms (I-V, X, and XI) and ubiquitous isoforms (VI-M) based on their expression patterns. Syt-I, a neuron-specific and abundant isoform, has been well characterized and postulated to be the exocytotic Ca2+ sensor. However, the functions of other isoforms remain obscure. Here, we report that ubiquitous isoforms of synaptotagmins, Syt-VII, Syt-VIII, and Syt-IX interacted with a cytoplasmic RNA-binding protein, SYNCRIP (Synaptotagmin-binding, cytoplasmic RNA-interacting protein), through their C2B domains. SYNCRIP was originally found in the Syt-II C2AB domain bound fraction from the mouse brain lysate, cDNA cloning of SYNCRIP cDNA revealed that the protein was highly homologous to heterogeneous nuclear ribonucleoprotein R (hnRNP R) recently identified. SYNCRIP protein was ubiquitously and constantly expressed in various tissues of mice parallel to hnRNP R, SYNCRIP indeed bound RNA with preference to poly(A) RNA; however, in contrast to the nuclear localization of hnRNP R, SYNCRIP was distributed predominantly in the cytoplasm as judged by both biochemical fractionation and immunohistochemical studies. In vitro binding experiments showed the potential interaction of SYNCRIP with C2B domains of Syts except for those of Syt-V, -VI, and -X. Furthermore, the interaction between SYNCRIP and Syt-VII, -VIII, or -IX was revealed by coimmunoprecipitation experiments using COS cells transiently expressing each Syt isoform, These findings suggested that SYNCRIP was a target of ubiquitous type of Syts and implied the involvement of ubiquitous Syts in the regulation of dynamics of the cytoplasmic mRNA.