Bjørnestad Synne Arstad, Guadagno Noemi Antonella, Kjos Ingrid, Progida Cinzia
Department of Biosciences, University of Oslo, 0316 Oslo, Norway.
iScience. 2022 Apr 14;25(5):104250. doi: 10.1016/j.isci.2022.104250. eCollection 2022 May 20.
Rab proteins are well known regulators of intracellular trafficking; however, more and more studies point to their function also in other cellular processes, including cell migration. In this work, we have performed an siRNA screen to identify Rab proteins that influence cell migration. The screen revealed Rab33b as the strongest candidate that affected cell motility. Rab33b has been previously reported to localize at the Golgi apparatus to regulate Golgi-to-ER retrograde trafficking and Golgi homeostasis. We revealed that Rab33b also mediates post-Golgi transport to the plasma membrane. We further identified Exoc6, a subunit of the exocyst complex, as an interactor of Rab33b. Moreover, our data indicate that Rab33b regulates focal adhesion dynamics by modulating the delivery of cargo such as integrins to focal adhesions. Altogether, our results demonstrate a role for Rab33b in cell migration by regulating the delivery of integrins to focal adhesions through the interaction with Exoc6.
Rab蛋白是细胞内运输的著名调节因子；然而，越来越多的研究表明它们在包括细胞迁移在内的其他细胞过程中也发挥作用。在这项研究中，我们进行了一项siRNA筛选，以鉴定影响细胞迁移的Rab蛋白。筛选结果显示，Rab33b是影响细胞运动性的最强候选蛋白。此前有报道称，Rab33b定位于高尔基体，调节高尔基体到内质网的逆行运输和高尔基体稳态。我们发现Rab33b还介导高尔基体后向质膜的运输。我们进一步鉴定出Exoc6，即外泌体复合物的一个亚基，作为Rab33b的相互作用蛋白。此外，我们的数据表明，Rab33b通过调节诸如整合素等货物向粘着斑的运输来调节粘着斑动力学。总之，我们的结果证明Rab33b通过与Exoc6相互作用调节整合素向粘着斑的运输，从而在细胞迁移中发挥作用。
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