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ATP13A2 deficiency disrupts lysosomal polyamine export 期刊论文
NATURE, 2020, 578 (7795) : 419-+
作者:  Nienhuis, J. H.;  Ashton, A. D.;  Edmonds, D. A.;  Hoitink, A. J. F.;  Kettner, A. J.;  Rowland, J. C.;  Tornqvist, T. E.
收藏  |  浏览/下载:6/0  |  提交时间:2020/07/03

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. 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. ATP13A2 promotes the cellular uptake of polyamines by endocytosis and transports them into the cytosol, highlighting a role for endolysosomes in the uptake of polyamines into cells. At high concentrations polyamines induce cell toxicity, which is exacerbated by ATP13A2 loss due to lysosomal dysfunction, lysosomal rupture and cathepsin B activation. This phenotype is recapitulated in neurons and nematodes with impaired expression of ATP13A2 or its orthologues. We present defective lysosomal polyamine export as a mechanism for lysosome-dependent cell death that may be implicated in neurodegeneration, and shed light on the molecular identity of the mammalian polyamine transport system.


The lysosomal polyamine transporter ATP13A2 controls the cellular polyamine content, and impaired lysosomal polyamine export represents a lysosome-dependent cell death pathway that may be implicated in ATP13A2-associated neurodegeneration.


  
Inter-hemispheric differences in energy budgets and cross-equatorial transport anomalies during the 20th century 期刊论文
CLIMATE DYNAMICS, 2019, 53: 115-135
作者:  Lembo, Valerio;  Folini, Doris;  Wild, Martin;  Lionello, Piero
收藏  |  浏览/下载:6/0  |  提交时间:2019/11/26
Global energy budget  Cross-equatorial heat transports  GHG forcing  CMIP5 historical simulations  
The role of El Nino in the global energy redistribution: a case study in the mid-Holocene 期刊论文
CLIMATE DYNAMICS, 2019, 52 (12) : 7135-7152
作者:  Saint-Lu, Marion;  Braconnot, Pascale;  Leloup, Julie;  Marti, Olivier
收藏  |  浏览/下载:10/0  |  提交时间:2019/11/26
El Nino  Energy redistribution  Transports  Fluxes  Mid-Holocene  Interannual variability  
Moisture transport by Atlantic tropical cyclones onto the North American continent 期刊论文
CLIMATE DYNAMICS, 2017, 48
作者:  Xu, Guangzhi;  Osborn, Timothy J.;  Matthews, Adrian J.
收藏  |  浏览/下载:4/0  |  提交时间:2019/04/09
Tropical cyclone  Moisture transports  Hydrological cycle  
Energy budgets and transports: global evolution and spatial patterns during the twentieth century as estimated in two AMIP-like experiments 期刊论文
CLIMATE DYNAMICS, 2017, 48
作者:  Lembo, Valerio;  Folini, Doris;  Wild, Martin;  Lionello, Piero
收藏  |  浏览/下载:6/0  |  提交时间:2019/04/09
Global energy budget  Meridional energy transports  Aerosol forcing  ERA-20CM  
Reconstruction of transports through the Strait of Gibraltar from limited observations 期刊论文
CLIMATE DYNAMICS, 2017, 48
作者:  Jorda, G.;  Sanchez-Roman, A.;  Gomis, D.
收藏  |  浏览/下载:1/0  |  提交时间:2019/04/09
Gibraltar Strait  Mediterranean Sea  Transports  Reconstruction