The Parkinson-associated human P5B-ATPase ATP13A2 increases the spermidine uptake

DE LA HERA, DIEGO P.; CORRADI, GERARDO R.; ADAMO, HUGO P.; DE TEZANOS PINTO, FELICITAS

BIOCHEMICAL JOURNAL

PORTLAND PRESS LTD

Lugar: Londres; Año: 2013 vol. 450 p. 47 - 53

0264-6021

P-type ion pumps are membrane transporters that have been classified into five subfamilies termed P1-P5. The ion transported by the P5-ATPases is not known. Five genes named ATP13A1-ATP13A5 that belong to the P5-ATPase group have been identified in humans. Mutations of the human gene ATP13A2 underlie a form of Parkinson?s disease (PD). Previous studies have suggested a relation between polyamines and P5B-ATPases. We have recently shown that the cytotoxicity induced by the polyamine analog paraquat (1,1´-dimethyl-4,4´-bipyridinium), which is an environmental agent related to PD development, was increased in ATP13A2-expressing CHO cells. Here we show that ATP13A2-expressing CHO cells exhibit two-fold higher accumulation of spermidine. Increasing concentrations of spermidine reduced the viability of CHO cells stably expressing the ATP13A2. The higher levels of spermidine attained by the ATP13A2-expressing CHO cells were correlated with the increase in the ATP-dependent spermidine uptake in an isolated subcellular fraction containing lysosomes and late endosomes. These results support the idea that the human P5B-ATPase ATP13A2 is involved in polyamine uptake.