The Spir actin organizers are involved in vesicle transport processes
The Spir actin organizers are involved in vesicle transport processes
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DOI：
10.1016/s0960-9822(01)00602-9
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发表时间：
2001-12-11
期刊：
影响因子：
9.2
通讯作者：
Pepperkok, R
中科院分区：
文献类型：
--
作者：
Kerkhoff, E;Simpson, JC;Pepperkok, R
p150-Spir蛋白被发现是Jun N-末端激酶的磷酸化靶标，是果蝇卵母细胞极化的重要调节剂[1，2]。Spir蛋白在物种之间高度保守，并且属于参与肌动蛋白组织的Wiskott-Aldrich同源区2（WH 2）蛋白家族。Spir的C-末端区域编码与FYVE基序高度同源的锌指结构[2]。Spir家族蛋白之间具有高度同源性的区域位于修饰的FYVE结构域附近（N-末端），并被命名为“Spirbox”。“Spi盒与rabphilin-3A的一个区域具有序列相似性，该区域介导与小GTdR Rab 3A的相互作用[3]。NIH 3 T3细胞中p150-Spir和绿色荧光蛋白标记的Rab GTP酶的共表达揭示了Spir蛋白与Rab 11 GTP酶特异性共定位，Rab 11 GTP酶定位于反式高尔基体网络（TGN）、高尔基体后囊泡和再循环内体[4]。不同的Spir定位模式依赖于修饰的FYVE指状基序和Spir盒的完整性。小鼠Spir-1显性干扰突变体的过表达强烈抑制了水泡性口炎病毒G（VSV G）蛋白向质膜的转运。病毒蛋白质被捕获在膜结构中，主要与TGN标记物TGN 46共定位。我们的研究结果表明，Spir肌动蛋白组织者是有针对性的细胞内膜结构，其修改FYVE锌指，并参与囊泡运输过程提供了一个新的肌动蛋白组织和细胞内运输之间的联系。
The p150-Spir protein, which was discovered as a phosphorylation target of the Jun N-terminal kinase, is an essential regulator of the polarization of the Drosophila oocyte [1, 2]. Spir proteins are highly conserved between species and belong to the family of Wiskott-Aldrich homology region 2 (WH2) proteins involved in actin organization. The C-terminal region of Spir encodes a zinc finger structure highly homologous to FYVE motifs [2]. A region with high homology between the Spir family proteins is located adjacent (N-terminal) to the modified FYVE domain and is designated as "Spirbox." The Spir-box has sequence similarity to a region of rabphilin-3A, which mediates interaction with the small GTPase Rab3A [3]. Coexpression of p150-Spir and green fluorescent protein-tagged Rab GTPases in NIH 3T3 cells revealed that the Spir protein colocalized specifically with the Rab11 GTPase, which is localized at the trans-Golgi network (TGN), post-Golgi vesicles, and the recycling endosome [4]. The distinct Spir localization pattern was dependent on the integrity of the modified FYVE finger motif and the Spir-box. Overexpression of a mouse Spir-1 dominant interfering mutant strongly inhibited the transport of the vesicular stomatitis virus G (VSV G) protein to the plasma membrane. The viral protein was arrested in membrane structures, largely colocalizing with the TGN marker TGN46. Our findings that the Spir actin organizer is targeted to intracellular membrane structures by its modified FYVE zinc finger and is involved in vesicle transport processes provide a novel link between actin organization and intracellular transport.