CONICET | Buscador de Institutos y Recursos Humanos

The P-type ion pumps are membrane transporters energized by ATP-hydrolysis which are classified into five subfamilies termed P1-P5. ATP13A1-ATP13A5 genes that belong to this group have been identified in humans. Mutations of the ATP13A2 gene were associated with neurodegenerative diseases like Parkinson?s Disease, Neuronal Ceroid Llipofuscinosis (CNL12), Hereditary Spastic Paraplegia (SPG78), Amyotrophic Lateral Sclerosis and most recently with colorectal cancer. ATP13A2 is localized in lysosomes and late endosomes. Dysfunction of this protein diminishes the lysosomal protein degradation, the autophagic flux and the exosome externalization. We have previously shown that ATP13A2 expression diminishes the bis (monoacylglyceryl) phosphate (BMP) content, which is an essential phospholipid for lipid degradation and exosome biogenesis inside acidic compartments. By using SH-SY5Y cells overexpressing the human P5-ATP13A2 (ATP13A2) or an inactive mutant (ATP13A2-D508N), we investigated the expression and distribution of ABHD6 protein, which is responsible for BMP degradation. Through immunodetection analysis we found that ATP13A2 cells showed an increased expression of ABHD6. Moreover, treatment of cells with spermine -the recently found substrate of ATP13A2- increased the relocalization of ABHD6 towards the cytoplasm when analyzed by immunofluorescence microscopy. Preliminary results show that ATP13A2 cells showed a higher activity of glucocerebrosidase measured with the fluorogenic substrate 4-Methylumbelliferyl -glucophyranoside. Altogether these results suggest that ATP13A2 overexpression may be altering the lipid digestion process inside acidic organelles.