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Cd, Mn, Ni and Se toxicity to Saccharomyces cerevisiae lacking YPK9p the orthologue of human ATP13A2 |
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| Authors: | Karyn Schmidt Barbara Stiller David A Pearce |
| Institution: | a Center for Neural Development and Disease, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Box 645, Rochester, NY 14620, USA b Aab Institute of Biomedical Sciences, Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA c Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA d Institute of Human Genetics, University of Cologne, Cologne, Germany e Institute for Genetics, University of Cologne, Cologne, Germany |
| Abstract: | The Saccharomyces cerevisiae gene YPK9 encodes a putative integral membrane protein which is 58% similar and 38% identical in amino acid sequence to the human lysosomal P5B ATPase ATP13A2. Mutations in ATP13A2 have been found in patients with Kufor-Rakeb syndrome, a form of juvenile Parkinsonism. We report that Ypk9p localizes to the yeast vacuole and that deletion of YPK9 confers sensitivity for growth for cadmium, manganese, nickel or selenium. These results suggest that Ypk9p may play a role in sequestration of divalent heavy metal ions. Further studies on the function of Ypk9p/ATP13A2 may help to define the molecular basis of Kufor-Rakeb syndrome and provide a potential link to environmental factors such as heavy metals contributing to some forms of Parkinsonism. |
| Keywords: | ATP13A2 YPK9 Kufor-Rakeb syndrome Parkinsonism |
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