Parkinson's disease-associated human P5B-ATPase ATP13A2 increases spermidine uptake

Biochem J. 2013 Feb 15;450(1):47-53. doi: 10.1042/BJ20120739.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Endosomes / metabolism
  • Humans
  • Kinetics
  • Lysosomes / metabolism
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Proton-Translocating ATPases / genetics
  • Proton-Translocating ATPases / metabolism*
  • Spermidine / metabolism*
  • Temperature

Substances

  • ATP13A2 protein, human
  • Proton-Translocating ATPases
  • Spermidine