LRRK1 phosphorylation of Rab7 at S72 links trafficking of EGFR-containing endosomes to its effector RILP
LRRK1 phosphorylation of Rab7 at S72 links trafficking of EGFR-containing endosomes to its effector RILP
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DOI：
10.1242/jcs.228809
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发表时间：
2019-06-01
影响因子：
4
通讯作者：
Matsumoto, Kunihiro
中科院分区：
文献类型：
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作者：
Hanafusa, Hiroshi;Yagi, Takuya;Matsumoto, Kunihiro
配体诱导的表皮生长因子受体 (EGFR) 激活启动转运事件，将受体从细胞表面重新定位到细胞内的内吞区室。含有 EGFR 的内体被转运至溶酶体，并被动力蛋白-动力蛋白运动蛋白复合物降解。然而，这种依赖于货物的内体运输机制在很大程度上仍然未知。在这里，我们发现，GTP 结合的 Rab7 被内体膜上富含亮氨酸的重复激酶 1 (LRRK1) 在 S72 上磷酸化。这种磷酸化促进 Rab7（本文指 Rab7a）与其效应器 RILP 的相互作用，导致动力蛋白-动力蛋白复合物募集到 Rab7 阳性囊泡。这反过来又促进了动力蛋白驱动的含有 EGFR 的内体向核周区域的运输。这些发现揭示了调节内体特定货物运输的机制。
Ligand-induced activation of epidermal growth factor receptor (EGFR) initiates trafficking events that re-localize the receptor from the cell surface to intracellular endocytic compartments. EGFR-containing endosomes are transported to lysosomes for degradation by the dynein-dynactin motor protein complex. However, this cargo-dependent endosomal trafficking mechanism remains largely uncharacterized. Here, we show that GTP-bound Rab7 is phosphorylated on S72 by leucine-rich repeat kinase 1 (LRRK1) at the endosomal membrane. This phosphorylation promotes the interaction of Rab7 (herein referring to Rab7a) with its effector RILP, resulting in recruitment of the dynein-dynactin complex to Rab7-positive vesicles. This, in turn, facilitates the dynein-driven transport of EGFR-containing endosomes toward the perinuclear region. These findings reveal a mechanism regulating the cargo-specific trafficking of endosomes.