Synaptotagmin-like protein 5: a novel Rab27A effector with C-terminal tandem C2 domains
Synaptotagmin-like protein 5: a novel Rab27A effector with C-terminal tandem C2 domains
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DOI：
10.1016/s0006-291x(02)00320-0
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发表时间：
2002-05-10
影响因子：
3.1
通讯作者：
Mikoshiba, K
中科院分区：
文献类型：
--
作者：
Kuroda, TS;Fukuda, M;Mikoshiba, K
突触结合蛋白样蛋白1-4（Synaptotagmin-like protein 1-4，Slp 1 -4）是羧基末端型（C-type）串联C2蛋白的新成员，由于其氨基末端含有一个独特的同源结构域而被归类为与突触结合蛋白和Doc 2家族不同的一个亚家族。称为Slp同源结构域（SHD）。我们先前表明，SHD作为Rab 27 A的结合位点发挥功能，Rab 27 A与人噬血细胞综合征（Griscelli综合征）相关[J. Biol. Chem. 277（2002）9212; J. Biol. Chem. 277（2002）12432]。在本研究中，我们确定了一个新的Slp家族成员，Slp 5。与其他Slp家族成员相同，Slp 5的SHD在体外和完整细胞中优先与Rab 27 A的GTP结合形式相互作用，并且与Rab 3A和Rab 6A轻微相互作用，但不与测试的其他Rabs相互作用（Rab 1、Rab 2、Rab 4A、Rab 5A、Rab 7、Rab 8、Rab 9、Rab 10、Rab 11 A、Rab 17、Rab 18、Rab 20、Rab 22、Rab 23、Rab 25、Rab 28和Rab 37）。然而，与Slp家族的其他成员不同，Slp 5 mRNA的表达高度局限于人胎盘和肝脏。Slp 5蛋白的表达和Slp 5与Rab 27 A在小鼠肝脏中的体内结合通过免疫沉淀进一步证实。结果表明，Slp 5可能参与Rab 27 A依赖的特定组织中的膜运输。(C)2002 Elsevier Science（美国）。All rights reserved.
Synaptotagmin-like proteins 1-4 (Slp1-4) are new members of the carboxyl-terminal-type (C-type) tandem C2 proteins and are classified as a subfamily distinct from the synaptotagmin and the Doc2 families, because the Sip family contains a unique homology domain at the amino terminus. referred to as the Slp homology domain (SHD). We previously showed that the SHD functions as a binding site for Rab27A, which is associated with human hemophagocytic syndrome (Griscelli syndrome) [J. Biol. Chem. 277 (2002) 9212; J. Biol. Chem. 277 (2002) 12432]. In the present study, we identified a novel member of the Slp family, Slp5. The same as other Slp family members, the SHD of Slp5 preferentially interacted with the GTP-bound form of Rab27A and marginally with Rab3A and Rab6A, both in vitro and in intact cells, but not with other Rabs tested (Rab1, Rab2, Rab4A, Rab5A, Rab7, Rab8, Rab9, Rab10, Rab11A, Rab17, Rab18, Rab20, Rab22, Rab23, Rab25, Rab28, and Rab37). However, unlike other members of the Slp family, expression of Slp5 mRNA was highly restricted to human placenta and liver. Expression of Slp5 protein and in vivo association of Slp5 with Rab27A in the mouse liver were further confirmed by immunoprecipitation. The results suggest that Slp5 might be involved in Rab27A-dependent membrane trafficking in specific tissues. (C) 2002 Elsevier Science (USA). All rights reserved.