Abstract
Lysine acetylation is a reversible post-translational modification (PTM) that has been detected on thousands of proteins in nearly all cellular compartments. The role of this widespread 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 reported previously in any other cell type. We also mapped an acetylome of astrocytes infected with the brain parasite, Toxoplasma gondii. It has been shown that infection with T. gondii modulates host cell gene expression, including several lysine acetyltransferase (KAT) and deacetylase (KDAC) genes, suggesting that the host acetylome may also be altered during infection. In the T. gondii-infected astrocytes, we identified 34 proteins exhibiting 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.
Highlights
Astrocytes constitute a major subset of glial cells that carry out a wide variety of critical operations in the mammalian brain
As the most abundant type of cell in the mammalian brain, astrocytes carry out a variety of essential functions that include supporting synapse formation, synaptic transmission, and responding to neuronal stress
As previously reported for multiple cell types, we found that lysine acetylation of astrocyte proteins generally occurs in lysine-rich regions, with a significant enrichment for glycine and alanine at positions-1, -2, and-3 and positions +1, +2, and +5 for alanine only, as shown in Fig. 4A [27,28]
Summary
Astrocytes constitute a major subset of glial cells that carry out a wide variety of critical operations in the mammalian brain. It is well-established that astrocytes play a supportive role for neurons by providing metabolic support, releasing and taking up neurotransmitters, and PLOS ONE | DOI:10.1371/journal.pone.0117966. Astrocytes release cytokines and chemokines to modulate effector cells. Other intracellular microbes capable of infecting astrocytes include Listeria monocytogenes and Toxoplasma gondii [3,4,5], but how they may modulate astrocyte function has yet to be defined
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