INCREASED α/β HYDROLASE DOMAIN-CONTAINING 6 (ABHD6) PROTEIN EXPRESSION IN SH-SY5Y CELLS OVEREXPRESSING THE P5-ATP13A2

MARCOS, ALEJANDRA; RINALDI, DEBORA; FERREIRA GOMES, MARIELA; DE TEZANOS PINTO, FELICITAS

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

The P-type ion pumps are membrane transporters energized byATP-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 recentlywith colorectal cancer. ATP13A2 is localized in lysosomes and lateendosomes. Dysfunction of this protein diminishes the lysosomalprotein 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 cellsshowed an increased expression of ABHD6. Moreover, treatmentof cells with spermine -the recently found substrate of ATP1increased the relocalization of ABHD6 towards the cytoplasm whenanalyzed by immunofluorescence microscopy. Preliminary resultsshow that ATP13A2 cells showed a higher activity of glucocerebrosidase measured with the fluorogenic substrate 4-Methylumbelliferylβ-glucophyranoside. Altogether these results suggest that ATP13A2overexpression may be altering the lipid digestion process insIde acid organelles.