RESEARCH ARTICLE Proteome-Wide Lysine Acetylation in Cortical Astrocytes and Alterations That Occur during Infection with Brain Parasite Toxoplasma gondii

Lysine acetylation is a reversible post-translational modification (PTM) that has been de-tected on thousands of proteins in nearly all cellular compartments. The role of this wide-spread PTM has yet to be fully elucidated, but can impact protein localization, interactions, activity, and stability. Here we present the first proteome-wide survey of lysine acetylation in cortical astrocytes, a subtype of glia that is a component of the blood-brain barrier and a key regulator of neuronal function and plasticity. We identified 529 lysine acetylation sites across 304 proteins found in multiple cellular compartments that largely function in RNA processing/transcription, metabolism, chromatin biology, and translation. Two hundred and seventy-seven of the acetylated lysines we identified on 186 proteins have not been re-ported previously in any other cell type. We also mapped an acetylome of astrocytes in-fected with the brain parasite, Toxoplasma gondii. It has been shown that infection with T. gondiimodulates host cell gene expression, including several lysine acetyltransferase (KAT) and deacetylase (KDAC) genes, suggesting that the host acetylome may also be al-tered during infection. In the T. gondii-infected astrocytes, we identified 34 proteins exhibit-ing a level of acetylation>2-fold and 24 with a level of acetylation<2-fold relative to uninfected astrocytes. Our study documents the first acetylome map for cortical astrocytes, uncovers novel lysine acetylation sites, and demonstrates that T. gondii infection produces an altered acetylome