title: Parkinson's disease-associated human P5B-ATPase ATP13A2 increases spermidine uptake.
abstract: 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, ATP13A (ATPase type 13A) 1-ATP13A5, that belong to the P5-ATPase group have been identified in humans. Mutations of the human gene ATP13A2 underlie a form of PD (Parkinson's disease). Previous studies have suggested a relation between polyamines and P5B-ATPases. We have recently shown that the cytotoxicity induced by the polyamine analogue paraquat (1,1'-dimethyl-4,4'-bipyridinium), which is an environmental agent related to PD development, was increased in ATP13A2-expressing CHO (Chinese-hamster ovary) cells. In the present study we showed that ATP13A2-expressing CHO cells exhibit a 2-fold higher accumulation of spermidine. Increasing concentrations of spermidine reduced the viability of CHO cells stably expressing ATP13A2. The higher levels of spermidine attained by the ATP13A2-expressing CHO cells were correlated with an increase in the ATP-dependent spermidine uptake in an isolated subcellular fraction containing lysosomes and late endosomes. The results of the present study support the idea that the human P5B-ATPase ATP13A2 is involved in polyamine uptake.
authors.affiliation: IQUIFIB (Instituto de Química y Fisicoquímica Biológicas), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.
authors.forename: Diego P
authors.initials: DP
authors.lastname: De La Hera
authors.forename: Gerardo R
authors.initials: GR
authors.lastname: Corradi
authors.forename: Hugo P
authors.initials: HP
authors.lastname: Adamo
authors.forename: Felicitas
authors.initials: F
authors.lastname: De Tezanos Pinto
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D013095:Spermidine / Q000378:metabolism*; D013696:Temperature
chemical_list: C514983:ATP13A2 protein, human; D006180:Proton-Translocating ATPases; D013095:Spermidine