![]() |
|
|
Center for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Deakin University, Burwood, Victoria, Australia
2To whom correspondence should be addressed. E-mail: dkramer{at}deakin.edu.au.
ABSTRACT
The final steps in the absorption and excretion of copper at the molecular level are accomplished by 2 closely related proteins that catalyze the ATP-dependent transport of copper across the plasma membrane. These proteins, ATP7A and ATP7B, are encoded by the genes affected in human genetic copper-transport disorders, namely, Menkes and Wilson diseases. We studied the effect of copper perfusion of an isolated segment of the jejunum of ATP7A transgenic mice on the intracellular distribution of ATP7A by immunofluorescence of frozen sections. Our results indicate that ATP7A is retained in the trans-Golgi network under copper-limiting conditions, but relocalized to a vesicular compartment adjacent to the basolateral membrane in intestines perfused with copper. The findings support the hypothesis that the basolateral transport of copper from the enterocyte into the portal blood may involve ATP7A pumping copper into a vesicular compartment followed by exocytosis to release the copper, rather than direct pumping of copper across the basolateral membrane.
KEY WORDS: dietary copper copper absorption transgenic mice ATP7A intestine
This article has been cited by other articles:
![]() |
B.-X. Ke, R. M. Llanos, and J. F. B. Mercer ATP7A Transgenic and Nontransgenic Mice Are Resistant to High Copper Exposure J. Nutr., April 1, 2008; 138(4): 693 - 697. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Linz, N. L. Barnes, A. M. Zimnicka, J. H. Kaplan, B. Eipper, and S. Lutsenko Intracellular targeting of copper-transporting ATPase ATP7A in a normal and Atp7b / kidney Am J Physiol Renal Physiol, January 1, 2008; 294(1): F53 - F61. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. G. Holloway, R. Grabski, T. Szul, M. L. Styers, J. A. Coventry, A. P. Monaco, and E. Sztul Activation of ADP-ribosylation factor regulates biogenesis of the ATP7A-containing trans-Golgi network compartment and its Cu-induced trafficking Am J Physiol Cell Physiol, December 1, 2007; 293(6): C1753 - C1767. [Abstract] [Full Text] [PDF] |
||||
![]() |
P de Bie, P Muller, C Wijmenga, and L W J Klomp Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes J. Med. Genet., November 1, 2007; 44(11): 673 - 688. [Abstract] [Full Text] [PDF] |
||||
![]() |
B.-E. Kim and M. J Petris Phenotypic diversity of Menkes disease in mottled mice is associated with defects in localisation and trafficking of the ATP7A protein J. Med. Genet., October 1, 2007; 44(10): 641 - 646. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Lutsenko, N. L. Barnes, M. Y. Bartee, and O. Y. Dmitriev Function and Regulation of Human Copper-Transporting ATPases Physiol Rev, July 1, 2007; 87(3): 1011 - 1046. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Nyasae, R. Bustos, L. Braiterman, B. Eipper, and A. Hubbard Dynamics of endogenous ATP7A (Menkes protein) in intestinal epithelial cells: copper-dependent redistribution between two intracellular sites Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G1181 - G1194. [Abstract] [Full Text] [PDF] |
||||
![]() |
B.-X. Ke, R. M. Llanos, M. Wright, Y. Deal, and J. F. B. Mercer Alteration of copper physiology in mice overexpressing the human Menkes protein ATP7A Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2006; 290(5): R1460 - R1467. [Abstract] [Full Text] [PDF] |
||||