Zinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-mediated proteostasis at the ER-Golgi interface.

Many secretory enzymes acquire essential zinc ions (Zn) in the Golgi complex. ERp44, a chaperone operating in the early secretory pathway, also binds Zn to regulate its client binding and release for the control of protein traffic and homeostasis. Notably, three membrane transporter complexes, ZnT4, ZnT5/ZnT6 and ZnT7, import Zn into the Golgi lumen in exchange with protons.

Quantitative Imaging of Labile Zn in the Golgi Apparatus Using a Localizable Small-Molecule Fluorescent Probe.

Fluorescent Zn probes used for the quantitative analysis of labile Zn concentration ([Zn]) in target organelles are crucial for understanding the role of Zn in biological processes. Although several fluorescent Zn probes have been developed to date, there is still a lack of consensus concerning the [Zn] in intracellular organelles. In this study, we describe the development of ZnDA-1H, a small-molecule fluorescent probe for Zn, which exhibits less pH sensitivity, high Zn selectivity, and large fluorescence enhancement upon binding to Zn.

Zinc regulates ERp44-dependent protein quality control in the early secretory pathway.

Zinc ions (Zn) are imported into the early secretory pathway by Golgi-resident transporters, but their handling and functions are not fully understood. Here, we show that Zn binds with high affinity to the pH-sensitive chaperone ERp44, modulating its localization and ability to retrieve clients like Ero1α and ERAP1 to the endoplasmic reticulum (ER). Silencing the Zn transporters that uptake Zn into the Golgi led to ERp44 dysfunction and increased secretion of Ero1α and ERAP1.