The phosphoinositide-associated protein Rush hour regulates endosomal trafficking in Drosophila.
The phosphoinositide-associated protein Rush hour regulates endosomal trafficking in Drosophila.
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DOI：
10.1091/mbc.e11-02-0154
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发表时间：
2012-02
影响因子：
3.3
通讯作者：
Wodarz A
中科院分区：
文献类型：
--
作者：
Gailite I;Egger-Adam D;Wodarz A
FYVE 结构域蛋白 Rush hour (Rush) 直接与 3-磷酸磷脂酰肌醇和二磷酸鸟苷解离抑制剂结合。它与 Rab7 和 Hrs 共定位，并且rush无效突变与 Rab5、Gdi、hrs 和康乃馨（果蝇 Vps33 同源物）的突变在遗传上相互作用。 Rush 过表达阻断了从晚期内体到溶酶体的转变，表明 Rush 在 Rab 的调节中具有功能。内吞作用调节多种细胞过程，包括质膜的蛋白质组成、细胞间信号传导和细胞极性。我们鉴定了高度保守的蛋白 Rush hour (Rush)，并表明它参与内吞作用的调节。 Rush 通过其 FYVE（Fab1p、YOTB、Vac1p、EEA1）结构域与磷脂酰肌醇 3-磷酸直接结合来定位于核内体。 Rush 还直接与 Rab GDP 解离抑制剂 (Gdi) 结合，后者参与 Rab 蛋白的激活。纯合的灯心草突变果蝇是可行的，但显示出与 Gdi、Rab5、hrs 和康乃馨（Vps33 的果蝇同源物）突变的遗传相互作用。 Rush 的过度表达会破坏内吞货物的进展并增加晚期内体的大小。 Rush 过表达细胞中溶酶体标记染色减少，表明晚期内体和溶酶体之间的过渡存在缺陷。 Rush 还可能导致内体簇的形成，可能是通过与 C 类 Vps/同型融合和液泡蛋白分选 (HOPS) 复合物相互作用影响内体融合。这些结果表明，Rush 通过调节 Rab 蛋白的活性来控制从早期内体到晚期内体以及从晚期内体到溶酶体的运输。
The FYVE-domain protein Rush hour (Rush) binds directly to phosphatidylinositol 3-phosphate and to guanosine diphosphate dissociation inhibitor. It colocalizes with Rab7 and Hrs, and a rush null mutation interacts genetically with mutations in Rab5, Gdi, hrs, and carnation, the fly Vps33 homologue. Rush overexpression blocks the transition from late endosomes to lysosomes, pointing to a function for Rush in regulation of Rabs. Endocytosis regulates multiple cellular processes, including the protein composition of the plasma membrane, intercellular signaling, and cell polarity. We have identified the highly conserved protein Rush hour (Rush) and show that it participates in the regulation of endocytosis. Rush localizes to endosomes via direct binding of its FYVE (Fab1p, YOTB, Vac1p, EEA1) domain to phosphatidylinositol 3-phosphate. Rush also directly binds to Rab GDP dissociation inhibitor (Gdi), which is involved in the activation of Rab proteins. Homozygous rush mutant flies are viable but show genetic interactions with mutations in Gdi, Rab5, hrs, and carnation, the fly homologue of Vps33. Overexpression of Rush disrupts progression of endocytosed cargo and increases late endosome size. Lysosomal marker staining is decreased in Rush-overexpressing cells, pointing to a defect in the transition between late endosomes and lysosomes. Rush also causes formation of endosome clusters, possibly by affecting fusion of endosomes via an interaction with the class C Vps/homotypic fusion and vacuole protein-sorting (HOPS) complex. These results indicate that Rush controls trafficking from early to late endosomes and from late endosomes to lysosomes by modulating the activity of Rab proteins.