Abstract
The Golgi apparatus is a membrane organelle located in the center of the protein processing and trafficking pathway. It consists of sub-compartments with distinct biochemical compositions and functions. Main functions of the Golgi, including membrane trafficking, protein glycosylation, and sorting, require a well-maintained stable microenvironment in the sub-compartments of the Golgi, along with metal ion homeostasis. Metal ions, such as Ca2+, Mn2+, Zn2+, and Cu2+, are important cofactors of many Golgi resident glycosylation enzymes. The homeostasis of metal ions in the secretory pathway, which is required for proper function and stress response of the Golgi, is tightly regulated and maintained by transporters. Mutations in the transporters cause human diseases. Here we provide a review specifically focusing on the transporters that maintain Golgi metal ion homeostasis under physiological conditions and their alterations in diseases.
Highlights
The Golgi apparatus is an organelle found in most eukaryotic cells
One unique characteristic of the Golgi is the multilayer stack that divides the Golgi membrane system into several sub-compartments known as cis, medial, and trans-Golgi, each of which contains a set of glycosylation enzymes that sequentially remove or add various sugar monomers to proteins as they pass through the Golgi
Once transported from the blood circulation into the cell by the membrane-localized high affinity copper uptake protein 1/SLC31A1, the Cu ion associates with the copper transport protein ATOX1, which transfers it to copper-transporting ATPase-1 (ATP7A) and -2 (ATP7B) on the Golgi membrane
Summary
The Golgi apparatus is an organelle found in most eukaryotic cells. Being part of the endomembrane system in the cytoplasm, it resides at the intersection of the exocytic and endocytic pathways, and works mainly in post-translational modifications and sorting of lipids and proteins. The Golgi is equipped with all the molecular components necessary for maintaining Ca2+ homeostasis in the Golgi lumen: Ca2+ ATPases that pump Ca2+ into the Golgi lumen, Ca2+ channels that release Ca2+ into the cytoplasm, and Ca2+-binding proteins that buffer Ca2+ in the Golgi lumen With all these regulators in action, the distinct sub-compartments of the Golgi appear to have a decreasing lumenal Ca2+ concentration through heterogenous expression of Ca2+ transporters and channels: the cis-Golgi expresses mainly SERCA and IP3Rs and contains around 250 μM lumenal Ca2+; the medial G6oolfg1i7 mainly expresses SERCA and SPCA1; and the trans-Golgi mainly expresses SPCA1 and RyRs, with a lumenal Ca2+ of about 130 μM (Figure 1) [29]. Maintenance of cellular Cu homeostasis is critical for cell function and survival [147]
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