The members of the Rab family of small GTPases are molecular switches that regulate distinct steps in different membrane traffic pathways. In addition to this canonical function, Rabs can play a role in other processes, such as cell adhesion and motility. Here, we reveal the role of the small GTPase Rab18 as a positive regulator of directional migration in chemotaxis, and the underlying mechanism. We show that knockdown of Rab18 reduces the size of focal adhesions (FAs) and influences their dynamics. Furthermore, we found that Rab18, by directly interacting with the endoplasmic reticulum (ER)-resident protein kinectin-1, controls the anterograde kinesin-1–dependent transport of the ER required for the maturation of nascent FAs and protrusion orientation toward a chemoattractant. Altogether, our data support a model in which Rab18 regulates kinectin-1 transport toward the cell surface to form ER–FA contacts, thus promoting FA growth and cell migration during chemotaxis.

中文翻译：

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Rab18 通过与内质网的 kinectin-1 相互作用来调节粘着斑动力学

小 GTP 酶 Rab 家族的成员是调节不同膜运输途径中不同步骤的分子开关。除了这种典型功能外，Rab 还可以在其他过程中发挥作用，例如细胞粘附和运动。在这里，我们揭示了小 GTPase Rab18 作为趋化定向迁移的正调节因子的作用及其潜在机制。我们发现 Rab18 的敲低可减小粘着斑 (FA) 的大小并影响其动态。此外，我们发现 Rab18 通过直接与内质网 (ER) 驻留蛋白 kinectin-1 相互作用，控制新生 FA 成熟和向化学引诱剂突出方向所需的 ER 顺行驱动蛋白-1 依赖性运输。总而言之，我们的数据支持这样一个模型：Rab18 调节 kinectin-1 向细胞表面的运输以形成 ER-FA 接触，从而促进趋化过程中 FA 的生长和细胞迁移。