ATP13A2 deficiency disrupts lysosomal polyamine export

Topic: Brain proteins, microglia and lab models

ATP13A2 (PARK9) is a late endolysosomal transporter that is genetically implicated in a spectrum of neurodegenerative disorders, including Kufor-Rakeb syndrome-a parkinsonism with dementia 1 -and early-onset Parkinson's disease 2 . ATP13A2 offers protection against genetic and environmental risk factors of Parkinson's disease, whereas loss of ATP13A2 compromises lysosomes 3 . However, the transport function of ATP13A2 in lysosomes remains unclear.

@article{vanveen2020-31996848,
  author  = {van Veen, S. and Martin, S. and Van den Haute, C. and Benoy, V. and Lyons, J. and Vanhoutte, R. and Kahler, J. P. and Decuypere, J. P. and others},
  title   = {{ATP13A2 deficiency disrupts lysosomal polyamine export}},
  journal = {Nature},
  year    = {2020},
  doi     = {10.1038/s41586-020-1968-7},
  pmid    = {31996848},
  url     = {https://doi.org/10.1038/s41586-020-1968-7}
}

Key findings

• ATP13A2 offers protection against genetic and environmental risk factors of Parkinson's disease, whereas loss of ATP13A2 compromises lysosomes 3 .
• However, the transport function of ATP13A2 in lysosomes remains unclear.
• Here we establish ATP13A2 as a lysosomal polyamine exporter that shows the highest affinity for spermine among the polyamines examined.
• Polyamines stimulate the activity of purified ATP13A2, whereas ATP13A2 mutants that are implicated in disease are functionally impaired to a degree that correlates with the disease phenotype.

Why it matters

This study found that the ATP13A2 protein acts as a lysosomal exporter of polyamines, especially spermine, and that disease-linked mutants of this protein work poorly. The work concerns Parkinson's disease and related disorders, not Alzheimer's disease, and does not test any treatment, cure, or prevention for Alzheimer's.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1038/s41586-020-1968-7
• PubMed: 31996848
• Original source →
• Free full text: Lirias (KU Leuven) →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

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