During C. elegans larval development, an inductive signal mediated by LET-23 EGFR (Epidermal Growth Factor Receptor) specifies three of six vulva precursor cells (VPCs) to adopt vulval cell fates. An evolutionarily conserved complex consisting of PDZ domain-containing scaffold proteins LIN-2 (CASK), LIN-7 (Lin7 or Veli), and LIN-10 (APBA1 or Mint1) (LIN-2/7/10) mediates basolateral LET-23 EGFR localization in the VPCs to permit signal transmission and development of the vulva. We recently found that the LIN-2/7/10 complex likely forms at Golgi ministacks; however, the mechanism through which the complex targets the receptor to the basolateral membrane remains unknown. Here we found that overexpression of LIN-10 or LIN-7 can compensate for loss of their complex components by promoting LET-23 EGFR signaling through previously unknown complex-independent and receptor-dependent pathways. In particular, LIN-10 can independently promote basolateral LET-23 EGFR localization, and its complex-independent function uniquely requires its PDZ domains that also regulate its localization to Golgi. These studies point to a novel complex-independent function for LIN-7 and LIN-10 that broadens our understanding of how this complex regulates targeted sorting of membrane proteins.

在C. elegans期间幼虫发育，由 LET-23 EGFR（表皮生长因子受体）介导的诱导信号指定六个外阴前体细胞 (VPC) 中的三个采用外阴细胞命运。由含有 PDZ 结构域的支架蛋白 LIN-2 (CASK)、LIN-7 (Lin7 或 Veli) 和 LIN-10 (APBA1 或 Mint1) (LIN-2/7/10) 组成的进化保守复合物介导基底外侧 LET- 23 EGFR 在 VPC 中的定位允许外阴的信号传输和发育。我们最近发现 LIN-2/7/10 复合体可能在高尔基体小堆栈中形成；然而，复合物将受体靶向基底外侧膜的机制仍然未知。在这里，我们发现 LIN-10 或 LIN-7 的过表达可以通过以前未知的复合物独立和受体依赖途径促进 LET-23 EGFR 信号传导，从而补偿其复杂成分的损失。特别是，LIN-10 可以独立地促进基底外侧 LET-23 EGFR 定位，其复杂的独立功能独特地需要其 PDZ 结构域也调节其定位到高尔基体。这些研究指出了 LIN-7 和 LIN-10 的一种新的独立于复合物的功能，拓宽了我们对这种复合物如何调节膜蛋白靶向分选的理解。