Human Molecular Genetics, Vol 6, 409-416, Copyright © 1997 by Oxford University Press
HA Dierick, AN Adam, JF Escara-Wilke and TW Glover
We have generated polyclonal antibodies against the amino-terminal third of
the Menkes protein (ATP7A; MNK) by immunizing rabbits with a
histidine-tagged MNK fusion construct containing metal-binding domains 1-4.
The purified antibodies were used in Western analysis of cell lysates and
in indirect immunofluorescence experiments on cultured cells. On Western
blots, the antibodies recognized the approximately 165 kDa MNK protein in
CHO cells and human fibroblasts. No MNK signal could be detected in
fibroblasts from a patient with Menkes disease or in Hep3B hepatocellular
carcinoma cells, confirming the specificity of the antibodies.
Immunocytochemical analysis of CHO cells and human fibroblasts showed a
distinct perinuclear signal corresponding to the pattern of the Golgi
complex. This staining pattern was similar to that of alpha-mannosidase II
which is a known resident enzyme of the Golgi complex. Using brefeldin A, a
fungal inhibitor of protein secretion, we further demonstrated that the MNK
protein is localized to the trans- Golgi network. This data provides direct
evidence for a subcellular localization of the MNK protein which is similar
to the proposed vacuolar localization of Ccc2p, the yeast homolog of MNK
and WND (ATP7B), the Wilson disease gene product. In light of the proposed
role of MNK both in subcellular copper trafficking and in copper efflux,
these data suggest a model for how these two processes are linked and
represent an important step in the functional analysis of the MNK protein.
ARTICLES
Immunocytochemical localization of the Menkes copper transport protein (ATP7A) to the trans-Golgi network
Department of Pediatrics, University of Michigan, Ann Arbor 48109-0618, USA.
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