The ADP-ribosylation factor 1 (Arf1) is involved in regulating copper uptake
Adam Southon, Mark Greenough, Ya Hui Hung, Melanie Norgate, Richard Burke, James Camakaris
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2011
Copper is a cofactor for many essential enzymes in aerobic organisms. When intracellular copper levels are elevated, the Menkes (ATP7A) P-Type ATPase traffics from the trans-Golgi network (TGN) towards the plasma membrane to facilitate copper efflux. The ADP-ribosylation factor 1 (Arf1) is required for maintenance of Golgi architecture and for vesicular trafficking, including the copper-responsive trafficking of ATP7A. Here we report an ATP7A-independent role of Arf1 in copper homeostasis. Whilst the loss of ATP7A function increased copper levels, RNA interference mediated Arf1 knockdown reduced copper accumulation in HeLa cells as well as in both wild-type and ATP7A-null cultured fibroblast..View full abstract
We gratefully acknowledge Dr. Sharon La Fontaine for providing the GM2069 and Me32a cell lines and the pJFM77 vector and Prof. Dennis Thiele for providing the Ctr1 antibody. The Australian Research Council and the Australian Institute of Nuclear Science and Engineering provided research grants. The J.C. Rowden White Trust provided a grant for partial funding of the Olympus Fluo View 1000 confocal microscope. Adam Southon is the recipient of a PhD scholarship from the National Health and Medical Research Council of Australia and the 2009 Dawson Bursary.