The multi-layered regulation of copper translocating P-type ATPases
The multi-layered regulation of copper translocating P-type ATPases
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DOI：
10.1007/s10534-008-9183-2
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发表时间：
2009-02-01
期刊：
影响因子：
3.5
通讯作者：
Camakaris, James
中科院分区：
文献类型：
--
作者：
Veldhuis, Nicholas A.;Gaeth, Ann P.;Camakaris, James
铜转位 Menkes（ATP7A、MNK 蛋白）和 Wilson（ATP7B、WND 蛋白）P 型 ATP 酶对于铜 (Cu) 稳态至关重要，在铜生物合成并入分泌途径的铜依赖性酶中发挥作用，通过铜外流进行铜解毒，以及全身性铜吸收 (MNK) 和铜排泄 (WND) 等特殊作用。这些功能的关键是它们在跨高尔基体网络 (TGN) 和位于顶端 (WND) 或基底外侧 (MNK) 细胞表面或附近的胞吐囊泡之间的铜和激素响应性分布。有趣的是，在同一组织中表达的 MNK 和 WND Cu-ATP 酶发挥着不同但互补的作用。虽然分子内差异可能决定了它们的不同作用，但预计细胞信号传导成分对于这些酶之间的差异和协同作用至关重要。本综述重点关注这些机制，包括影响 Cu-ATP 酶运输和双功能的细胞信号传导途径。据推测，磷酸化事件在铜稳态中发挥核心作用，促进铜酶和铜独立机制之间的多层调节和串扰。
The copper-translocating Menkes (ATP7A, MNK protein) and Wilson (ATP7B, WND protein) P-type ATPases are pivotal for copper (Cu) homeostasis, functioning in the biosynthetic incorporation of Cu into copper-dependent enzymes of the secretory pathway, Cu detoxification via Cu efflux, and specialized roles such as systemic Cu absorption (MNK) and Cu excretion (WND). Essential to these functions is their Cu and hormone-responsive distribution between the trans-Golgi network (TGN) and exocytic vesicles located at or proximal to the apical (WND) or basolateral (MNK) cell surface. Intriguingly, MNK and WND Cu-ATPases expressed in the same tissues perform distinct yet complementary roles. While intramolecular differences may specify their distinct roles, cellular signaling components are predicted to be critical for both differences and synergy between these enzymes. This review focuses on these mechanisms, including the cell signaling pathways that influence trafficking and bi-functionality of Cu-ATPases. Phosphorylation events are hypothesized to play a central role in Cu homeostasis, promoting multi-layered regulation and cross-talk between cuproenzymes and Cu-independent mechanisms.