How long do proteins and their modifications persist, and what can these lifetimes tell us about cellular function? This talk brings together two ways of measuring molecular turnover, protein lifetimes and the exchange of phosphate at individual sites in living cells.

First, I will describe how metabolic labeling, mass spectrometry and mathematical modeling allow us to measure protein lifetimes in vivo while accounting for amino acid recycling. These lifetimes differ systematically across brain regions and subcellular fractions. I will then introduce PulsPhos, which combines stable isotope labeling of phosphate with phosphoproteomics and modeling to follow phosphate exchange at individual sites. Phosphorylation lifetimes turn out to vary widely, even between sites on the same protein, and relate to the identity of the phosphorylated residue and to subcellular localization.

Throughout the talk, I will discuss the experimental and analytical choices that make these measurements interpretable. I will close by considering protein turnover and phosphorylation dynamics together. How can we distinguish the persistence of a protein from that of its modifications, and what does each contribute to the persistence of a signaling state? These questions are particularly relevant in the brain, where long-lived proteins support rapidly changing signals. Measuring both processes in the same preparation would be an important next step, and I look forward to discussing how we might get there.

 

場所：本セミナーはZoomで行います。

 

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理学系研究科 生物科学専攻 生物情報科学科 黒田研究室　 黒田 真也