HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Lutsenko, S. Articles by Dmitriev, O. Y. Search for Related Content PubMed PubMed Citation Articles by Lutsenko, S. Articles by Dmitriev, O. Y.

Function and Regulation of Human Copper-Transporting ATPases

Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, Oregon; and Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

Copper-transporting ATPases (Cu-ATPases) ATP7A and ATP7B are evolutionarily conserved polytopic membrane proteins with essential roles in human physiology. The Cu-ATPases are expressed in most tissues, and their transport activity is crucial for central nervous system development, liver function, connective tissue formation, and many other physiological processes. The loss of ATP7A or ATP7B function is associated with severe metabolic disorders, Menkes disease, and Wilson disease. In cells, the Cu-ATPases maintain intracellular copper concentration by transporting copper from the cytosol across cellular membranes. They also contribute to protein biosynthesis by delivering copper into the lumen of the secretory pathway where metal ion is incorporated into copper-dependent enzymes. The biosynthetic and homeostatic functions of Cu-ATPases are performed in different cell compartments; targeting to these compartments and the functional activity of Cu-ATPase are both regulated by copper. In recent years, significant progress has been made in understanding the structure, function, and regulation of these essential transporters. These studies raised many new questions related to specific physiological roles of Cu-ATPases in various tissues and complex mechanisms that control the Cu-ATPase function. This review summarizes current data on the structural organization and functional properties of ATP7A and ATP7B as well as their localization and functions in various tissues, and discusses the current models of regulated trafficking of human Cu-ATPases.

This article has been cited by other articles:

				M. Gonzalez-Guerrero and J. M. Arguello Mechanism of Cu+-transporting ATPases: Soluble Cu+ chaperones directly transfer Cu+ to transmembrane transport sites PNAS, April 22, 2008; 105(16): 5992 - 5997. [Abstract] [Full Text] [PDF]

				E. C. Madsen, P. A. Morcos, B. A. Mendelsohn, and J. D. Gitlin In vivo correction of a Menkes disease model using antisense oligonucleotides PNAS, March 11, 2008; 105(10): 3909 - 3914. [Abstract] [Full Text] [PDF]