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By Mark Tsechansky, Jeremy D. O'Connell, Rammohan Narayanaswamy, Andrew D. Ellington, and Edward Marcotte Protein aggregation in neurodegenerative and metabolic diseases is widely recognized, and the number of protein aggregation diseases continues to grow, suggesting that protein aggregation in-vivo maybe relatively common. In this study we aimed to decipher an intriguing phenomenon that was discovered recently in our lab - the widespread reorganization of hundreds of distinct soluble cytosolic proteins into punctate foci under starvation conditions. A key question is whether these proteins are organizing into functional assemblies or represent catastrophic aggregation. In support of aggregation, we provide evidence that shows foci-forming proteins are systematically elevated in aggregation potential while being diminished in codon optimality and expression levels. In support of functionality, we observe metabolite specific induction and dissolution of foci. There are diverse requirements for formation and dissolution, with diverse kinetics of formation, suggesting multiple mechanisms underlying foci formation of different proteins. We discuss possible interpretations and offer a model explaining these observations. |
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