Rsp5, the Nedd4 family member in yeast, is an E3 ubiquitin ligase involved in numerous cellular processes, many of which require Rsp5 to interact with PY-motif containing adaptor proteins. Here, we show that two paralogous transmembrane Rsp5 adaptors, Rcr1 and Rcr2, are sorted to distinct cellular locations: Rcr1 is a plasma membrane (PM) protein, whereas Rcr2 is sorted to the vacuole. Rcr2 is delivered to the vacuole using ubiquitin as a sorting signal. Rcr1 is delivered to the PM by the exomer complex using a newly uncovered PM sorting motif. Further, we show that Rcr1, but not Rcr2, is up-regulated via the calcineurin/Crz1 signaling pathway. Upon exogenous calcium treatment, Rcr1 ubiquitinates and down-regulates the chitin synthase Chs3. We propose that the PM-anchored Rsp5/Rcr1 ubiquitin ligase-adaptor complex can provide an acute response to degrade unwanted proteins under stress conditions, thereby maintaining cell integrity.

中文翻译：

---

质膜泛素连接酶 Rcr1 对内吞作用的钙调磷酸酶依赖性调节

Rsp5 是酵母中的 Nedd4 家族成员，是一种 E3 泛素连接酶，参与多种细胞过程，其中许多过程需要 Rsp5 与含有 PY 基序的接头蛋白相互作用。在这里，我们展示了两个旁系同源跨膜 Rsp5 接头 Rcr1 和 Rcr2 被分类到不同的细胞位置：Rcr1 是质膜 (PM) 蛋白，而 Rcr2 被分类到液泡。使用泛素作为分选信号将 Rcr2 递送至液泡。Rcr1 通过外显子复合体使用新发现的 PM 分选基序传递至 PM。此外，我们发现 Rcr1（而非 Rcr2）通过钙调神经磷酸酶/Crz1 信号通路上调。外源钙处理后，Rcr1 泛素化并下调几丁质合酶 Chs3。我们认为，PM 锚定的 Rsp5/Rcr1 泛素连接酶-适配器复合物可以提供急性反应，在应激条件下降解不需要的蛋白质，从而维持细胞完整性。