Further Insight into Zinc Homeostasis in Cells Unearthed by Researchers

A research group has revealed how zinc transporter complexes regulate the zinc ion (Zn²⁺) concentrations in different regions of the Golgi apparatus and revealed that this mechanism finely regulates the ERp44 chaperone protein.

The results have been published in the journal Nature Communications On May 9, 2023, he reveals the critical chemical and cellular biological mechanism that plays a role in zinc homeostasis, which is essential for avoiding fatal diseases such as diabetes, cancer, failure to thrive, and immunodeficiency.

As a trace element, zinc is essential to our health. Zn²⁺ It is vital for enzyme catalysis, protein folding, DNA binding, and regulation of gene expression, with approximately 10% of human protein binding zinc.²⁺ for their structural maturity and function.

Secretory proteins such as hormones, immunoglobulins, and blood clotting factors are synthesized in the endoplasmic reticulum (ER), which is a complex membranous network of tubules. Then, they are transported and matured in the Golgi apparatus, the organelle made up of several flat sacs called cisternae, which sort and process proteins before they are routed to a specific destination. Chaperone proteins are vital to maintaining protein homeostasis and preventing the formation of misfolded or aggregated proteins in these organelles.

The group’s previous research showed that Zn²⁺ The Golgi apparatus has an essential role in protein quality control in the early secretory pathway involving the ER and Golgi. This system is mediated by the ER-Golgi electric cycling protein ERp44.

There are three ZnT complexes in the Golgi apparatus: ZnT4, Znt5/6, and ZnT7. So far, the mechanics of how to use Zn²⁺ The maintenance of homeostasis in the Golgi apparatus has remained unclear.

“Using chemical and cell biology approaches together, we revealed that ZnT complexes regulate Zn²⁺ The concentrations are in the different golgi compartments, namely the cis, medial golgi cisterns, and trans golgi, says Kenji Inaba, corresponding author of the study and professor at the Interdisciplinary Research Institute for Advanced Materials Science at Tohoku University. Transport, localization, and function of ERp44 controlled by ZnT complexes. ”

ERp44 captures immature secreted proteins in the Golgi apparatus to prevent their abnormal secretion. Previous studies have shown that mice with suppressed ERp44 expression suffer from heart failure and hypotension.

In addition, several zinc secretory enzymes are associated with various diseases, including metastasis of cancer cells and hypophosphatemia. These enzymes depend on ZnT compounds residing in the Golgi to obtain Zn²⁺ for enzymatic activity. Male mice infected with ZnT5 experienced death from arrhythmias, so there is a possible link to zinc.²⁺ Homeostasis for cardiovascular disease.

“Our findings will help us understand the mechanism by which zinc is inactivated²⁺ Homeostasis in the early secretory pathway leads to the development of pathological conditions,” Inaba adds.

The group hopes that the strategies used in their study can paint a larger picture of the mechanisms behind the maintenance of intracellular zinc.²⁺ Homeostasis, and recommending future studies that could measure zinc²⁺ In other organelles such as mitochondria and nucleus.