The multi-layered regulation of copper translocating P-type ATPases

Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Nicholas A VeldhuisJames Camakaris

Abstract

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.

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Citations

Jul 16, 2009·The Journal of Biological Chemistry·Jack H Kaplan, Svetlana Lutsenko
Mar 1, 2011·Annual Review of Biophysics·Michael G Palmgren, Poul Nissen
Sep 12, 2014·Metallomics : Integrated Biometal Science·Jianbin WangRichard Burke
Apr 8, 2010·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Adam SouthonJames Camakaris
Jan 25, 2011·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·N A VeldhuisJ Camakaris
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Aug 2, 2013·Metallomics : Integrated Biometal Science·Adam SouthonJames Camakaris
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