The SH3p4/Sh3p8/SH3p13 protein family: Binding partners for synaptojanin and dynamin via a Grb2-like Src homology 3 domain
The SH3p4/Sh3p8/SH3p13 protein family: Binding partners for synaptojanin and dynamin via a Grb2-like Src homology 3 domain
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DOI：
10.1073/pnas.94.16.8569
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发表时间：
1997-08-05
影响因子：
11.1
通讯作者：
DeCamilli, P
中科院分区：
文献类型：
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作者：
Ringstad, N;Nemoto, Y;DeCamilli, P
GT3发动蛋白I和肌醇5磷酸酶synaptojanin是涉及突触囊泡再循环的神经末梢蛋白，两种蛋白都含有可与多种Src同源3（SH 3）结构域相互作用的COOH-末端富含脯氨酸的结构域，神经系统中发动蛋白I和synaptojanin的主要生理结合配偶体是两性物理蛋白I，一种也集中在神经末梢中的含有SH 3结构域的蛋白，我们利用synaptojanin富含脯氨酸的尾部，通过双杂交方法筛选大鼠脑文库，以鉴定synaptojanin的其他相互作用伙伴。分离出三种含有与Grb 2的SH 3结构域密切相关的SH 3结构域的相关蛋白：SH 3 p4、SH 3 p8和SH 3 p13。进一步的生物化学研究表明，SH 3 pC 1/8/13蛋白结合突触连接蛋白和发动蛋白I，SH 3 p4/8/13转录本在组织中差异表达：SH 3 p4 mRNA仅在引流管中检测到，SH 3 p13 mRNA在脑和睾丸中存在，SH 3 p8转录物在多个组织中以相似的水平检测到，发现SH 3 p4/8/13蛋白家族的成员集中在神经末梢中，并且从具有识别SH 3 p4/8/13的抗体的脑提取物中共沉淀出synaptojanin和发动蛋白I的池。这些发现强调了SH 3介导的相互作用在突触囊泡循环中的重要作用。
The GTPase dynamin I and the inositol 5 phosphatase synaptojanin are nerve terminal proteins implicated in synaptic vesicle recycling, Both proteins contain COOH-terminal proline-rich domains that can interact with a variety of Src homology 3 (SH3) domains, A major physiological binding partner for dynamin I and synaptojanin in the nervous system is amphiphysin I, an SH3 domain-containing protein also concentrated in nerve terminals, We have used the proline rich tail of synaptojanin to screen a rat brain library by the two-hybrid method to identify additional interacting partners of synaptojanin. Three related proteins containing SH3 domains that are closely related to the SH3 domains of Grb2 were isolated: SH3p4, SH3p8, and SH3p13. Further biochemical studies demonstrated that the SH3pc1/8/13 proteins bind to both synaptojanin and dynamin I, The SH3p4/8/13 transcripts are differentially expressed in tissues: SH3p4 mRNA was detected only in drain, SH3p13 mRNA was present in brain and testis, and the SH3p8 transcript was detected at similar levels in multiple tissues, Members of the SH3p4/8/13 protein family were found to be concentrated in nerve terminals, and pools of synaptojanin and dynamin I were coprecipitated from brain extracts with antibodies recognizing SH3p4/8/13. These findings underscore the important role of SH3-mediated interactions in synaptic vesicle recycling.