Is PARK9 protein a manganese transporter protein?

Parkinson Disease (PD) is a neurodegenerative pathology of yet un-clarified aetiology although genetics and risk factors like exposure to some pesticides or post-trauma may pre-dispose towards the development of certain types of PD. Lately it has emerged that exposure to manganese (i.e. in welders or miners) may cause a PD-like syndrome (Parkinsonism) therefore emphasising a connection between genetic and environmental causes of Parkinson's disease. Furthermore, a genetic interaction between two Parkinson's disease genes, namely alpha-synuclein and PARK9 (formerly known as ATP13A2) has been previously reported, and interestingly PARK9 protein can protect cells from manganese poisoning. Recent data have also shown that deletion of YPK9, a yeast gene 58% similar and 38% identical in its amino acid sequence to human PARK9, confers sensitivity to growth defects in the presence of cadmium, manganese, nickel and selenium suggesting that YPK9 protein may play a role in the sequestration of divalent heavy metal ions. One may argue that a mutation in PARK9 may similarly expose humans to these cations and especially to manganese. In this respect, we have chosen short fragments of YPK9 protein that included interesting sequences for metal binding and studied their behaviour towards divalent cations such as manganese and calcium, using NMR mono- and bidimensional techniques and EPR spectroscopy. A clear assessment of metal binding in the yeast analogue may shed light on what may happen in humans.