< Back to previous page

Project

Connecting polyamine transport in astrocytes to neurodevelopmental disorders via ATP13A4

During my FWO PhD fellowship, I proved that ATP13A2 works as a lysosomal polyamine exporter implicated in neurodegenerative disorders. Here, I will focus on a closely related isoform, ATP13A4, which is genetically associated with neurodevelopmental disorders. ATP13A4 is localized predominantly in astrocytes and according to my preliminary data may also function as a polyamine transporter. Polyamines are regulators of astrocyte functionality and neuronal modulation, but how polyamines are taken up by astrocytes remains unknown. I therefore hypothesize that ATP13A4 may mediate polyamine uptake in astrocytes, whereas ATP13A4 dysfunction may disturb polyamine homeostasis, ultimately leading to astrocyte and/or neuronal dysfunction underlying neurodevelopmental disorders. To test this hypothesis, I will use complementary biochemical and cellular assays to characterize the molecular properties of ATP13A4 wildtype and disease mutants. I will further assess the impact of Atp13a4 deficiency on astrocyte polyamine homeostasis, endosomal functionality and relevant astrocyte functions. To analyse the in vivo consequences of Atp13a4 deficiency, an astrocyte-specific Atp13a4 knock-out mouse strain will be generated to determine the impact of Atp13a4 on astrocyte/neuronal interplay and mouse behaviour. Understanding the physiological role of ATP13A4 in astrocytes and in the brain may validate ATP13A4 as a candidate therapeutic target for neurodevelopmental disorders. 
GENERAL
 

Date:1 Oct 2020 →  Today
Keywords:polyamine transport, neurodevelopmental disorders, astrocytes
Disciplines:Behavioural biology, Intracellular compartments and transport, Neurological and neuromuscular diseases, Cell physiology, Molecular physiology