SPIN90, an adaptor protein, alters the proximity between Rab5 and Gapex5 and facilitates Rab5 activation during EGF endocytosis.,Experimental & Molecular Medicine

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SPIN90, an adaptor protein, alters the proximity between Rab5 and Gapex5 and facilitates Rab5 activation during EGF endocytosis.
Experimental & Molecular Medicine ( IF 9.5 ) Pub Date : 2019-07-29 , DOI: 10.1038/s12276-019-0284-5
Hwan Kim ₁ , Hyejin Oh ₁ , Young Soo Oh ₁ , Jeomil Bae ₂ , Nan Hyung Hong ₃ , Su Jung Park ₁ , Suyeon Ahn ₁ , Miriam Lee ₁ , Sangmyung Rhee ₄ , Sung Haeng Lee ₅ , Youngsoo Jun ₁ , Sung Hyun Kim ₆ , Yun Hyun Huh ₁ , Woo Keun Song ₁

Affiliation

During ligand-mediated receptor endocytosis, the small GTPase Rab5 functions in vesicle fusion and trafficking. Rab5 activation is known to require interactions with its guanine nucleotide-exchange factors (GEFs); however, the mechanism regulating Rab5 interactions with GEFs remains unclear. Here, we show that the SH3-adapter protein SPIN90 participates in the activation of Rab5 through the recruitment of both Rab5 and its GEF, Gapex5, to endosomal membranes during epidermal growth factor (EGF)-mediated endocytosis. SPIN90 strongly interacts with the inactive Rab5/GDI2 complex through its C-terminus. In response to EGF signaling, extracellular signal-regulated kinase (ERK)-mediated phosphorylation of SPIN90 at Thr-242 enables SPIN90 to bind Gapex5 through its N-terminal SH3 domain. Gapex5 is a determinant of Rab5 membrane targeting, while SPIN90 mediates the interaction between Gapex5 and Rab5 in a phosphorylation-dependent manner. Collectively, our findings suggest that SPIN90, as an adaptor protein, simultaneously binds inactive Rab5 and Gapex5, thereby altering their spatial proximity and facilitating Rab5 activation.

中文翻译：

SPIN90 是一种衔接蛋白，可改变 Rab5 和 Gapex5 之间的接近程度，并在 EGF 内吞作用期间促进 Rab5 激活。

在配体介导的受体内吞作用过程中，小 GTP 酶 Rab5 在囊泡融合和运输中发挥作用。已知 Rab5 激活需要与其鸟嘌呤核苷酸交换因子 (GEF) 相互作用；然而，调节 Rab5 与 GEF 相互作用的机制仍不清楚。在这里，我们表明 SH3 衔接蛋白 SPIN90 通过在表皮生长因子 (EGF) 介导的内吞作用期间将 Rab5 及其 GEF Gapex5 募集到内体膜来参与 Rab5 的激活。SPIN90 通过其 C 端与非活性 Rab5/GDI2 复合物强烈相互作用。响应 EGF 信号，细胞外信号调节激酶 (ERK) 介导的 SPIN90 在 Thr-242 处的磷酸化使 SPIN90 能够通过其 N 末端 SH3 结构域结合 Gapex5。Gapex5 是 Rab5 膜靶向的决定因素，而 SPIN90 以磷酸化依赖的方式介导 Gapex5 和 Rab5 之间的相互作用。总的来说，我们的研究结果表明 SPIN90 作为衔接蛋白同时结合无活性的 Rab5 和 Gapex5，从而改变它们的空间接近度并促进 Rab5 激活。

更新日期：2019-07-29

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