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Review
. 2023 Nov 30:13:1267931.
doi: 10.3389/fcimb.2023.1267931. eCollection 2023.

The interplay between copper metabolism and microbes: in perspective of host copper-dependent ATPases ATP7A/B

Yixuan Zhou  1   2   3 , Leiliang Zhang  1   2   3
Affiliations
Review

The interplay between copper metabolism and microbes: in perspective of host copper-dependent ATPases ATP7A/B

V体育安卓版 - Yixuan Zhou et al. Front Cell Infect Microbiol. .

VSports app下载 - Abstract

Copper, a vital element in various physiological processes, is transported from the gastrointestinal tract to tissues and cells through diverse copper transporters. Among these transporters, ATP7A and ATP7B play significant roles in regulating systemic copper metabolism and exhibit precise regulation in their intracellular trafficking. These transporters undergo dynamic shuttling between the trans-Golgi network (TGN) and the plasma membrane via the endocytic recycling mechanism, which involves the retromer and other associated factors. Interestingly, the antimicrobial attribute of copper implies a potential connection between microbial infection and copper metabolism. Several microbes, including Salmonella enterica, Cryptococcus, Influenza A virus (IAV) and Zika virus (ZIKV) have been observed to impact the regulatory mechanisms of ATP7A/B, either directly or indirectly, as a means of survival. This review summarizes the key features and trafficking mechanisms of the copper transporters ATP7A/B, and examines the intricate interplay between microbes and copper metabolism. Ultimately, it highlights how microbes can perturb copper homeostasis through interactions with host factors, offering valuable insights into the mechanistic aspects of host-microbe interactions. VSports手机版.

Keywords: ATP7A; ATP7B; copper metabolism; membrane trafficking; microbes V体育安卓版. .

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Conflict of interest statement (V体育官网入口)

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest V体育ios版. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

V体育安卓版 - Figures

Figure 1
Figure 1
Function of ATP7A/B in systematic copper distribution and their domain structure. (A) Copper homeostasis is maintained largely by importer CTR1 and exporter ATP7A/B. Cu is absorbed in small intestine by enterocytes, through the apical CTR1, and the efflux is mediated by ATP7A, transporting Cu into blood vessels. After intake by CTR1 on hepatocytes, Cu is loaded on cuproproteins, including ceruloplasmin at TGN, or secreted to bile when redundant copper accumulating, which are both mediated by ATP7B. The lack of ATP7A/B would lead to different kinds of copper deficiency. (B) Schematic diagram of the membrane topology and main domains of the P1B-type ATPase, ATP7A/B. ATP7A/B contains an eight-helices transmembrane domain (marked blue) to form a pore, connecting with three cytoplasmic domains including A (marked purple), P (marked lemon), N (marked green). The N termini lies six MBDs (marked dark blue) and C termini contains a dileucine motif (marked green). For ATP7A, a class I PBM is located on the C terminus (DTAL).
Figure 2
Figure 2
Intracellular trafficking of ATP7A and a proposed model of inhibition of ATP7A trafficking by SARS-CoV-2 S. (A) In response to elevated copper levels, ATP7A undergoes relocation from TGN to the plasma membrane. This movement is facilitated by the interactions of ATP7A with AP-1 and PDZD11-PLEKHA.When overloaded copper is secreted, the ATP7A pump is wrapped in endosome. The endosome is then sorted, allowing it to either return back to TGN or be retrieved and transported back to the plasma membrane through SNX27-retromer sorting. (B) The endocytic recycling of ATP7A is facilitated by the interaction between SNX27-Vps26A and ATP7A. However, SARS-CoV-2 S protein could inhibit the targeting of ATP7A to the plasma membrane by binding with SNX27 through its PDZ binding sequence. This binding event may interfere with the normal recycling of ATP7A, ultimately leading to a decrease of ATP7A in cell surface.
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