Division of Endocrinology and Metabolism, Department of Medicine, and Department of Anatomy and Cell Biology, McGill University; and the Metabolic Disorders and Complications Program, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Division of Endocrinology and Metabolism, Department of Medicine, and Department of Anatomy and Cell Biology, McGill University; and the Metabolic Disorders and Complications Program, Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Development. 2021 Mar 5;148(5):dev194167. doi: 10.1242/dev.194167.
The evolutionarily conserved LIN-2 (CASK)/LIN-7 (Lin7A-C)/LIN-10 (APBA1) complex plays an important role in regulating spatial organization of membrane proteins and signaling components. In , the complex is essential for the development of the vulva by promoting the localization of the sole Epidermal growth factor receptor (EGFR) ortholog LET-23 to the basolateral membrane of the vulva precursor cells where it can specify the vulval cell fate. To understand how the LIN-2/7/10 complex regulates receptor localization, we determined its expression and localization during vulva development. We found that LIN-7 colocalizes with LET-23 EGFR at the basolateral membrane, whereas the LIN-2/7/10 complex colocalizes with LET-23 EGFR at cytoplasmic punctae that mostly overlap with the Golgi. Furthermore, LIN-10 recruits LIN-2, which in turn recruits LIN-7. We demonstrate that the complex forms with a particularly strong interaction and colocalization between LIN-2 and LIN-7, consistent with them forming a subcomplex. Thus, the LIN-2/7/10 complex forms on the Golgi on which it likely targets LET-23 EGFR trafficking to the basolateral membrane rather than functioning as a tether.
进化上保守的 LIN-2(CASK)/LIN-7(Lin7A-C)/LIN-10(APBA1)复合物在调节膜蛋白和信号成分的空间组织方面发挥着重要作用。在 中,该复合物通过促进唯一的表皮生长因子受体(EGFR)同源物 LET-23 到外阴前体细胞的基底外侧膜的定位,对于外阴的发育是必不可少的,在那里它可以指定外阴细胞命运。为了了解 LIN-2/7/10 复合物如何调节受体定位,我们在外阴发育过程中确定了其表达和定位。我们发现 LIN-7 与 LET-23 EGFR 在基底外侧膜处共定位,而 LIN-2/7/10 复合物与 LET-23 EGFR 在细胞质点状结构中共定位,这些点状结构主要与高尔基体重叠。此外,LIN-10 招募 LIN-2,而 LIN-2 又招募 LIN-7。我们证明该复合物形成 ,其中 LIN-2 和 LIN-7 之间具有特别强的相互作用和共定位,这与它们形成亚复合物一致。因此,LIN-2/7/10 复合物在高尔基体上形成,它可能将 LET-23 EGFR 靶向到基底外侧膜,而不是作为系链发挥作用。