Essential Genetic Interactors of Required for Spatial Sequestration and Asymmetrical Inheritance of Protein Aggregates

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Asymmetric cell division is key to cellular rejuvenation and budding yeast exploits this mode of cytokinesis to generate a young daughter cell from a mother cell that with each division grows progressively older. Thus, age physiognomies are reset in the progeny during division, a phenomenon that requires a mother-biased segregation of cytoplasmic ‘aging factors’, including damaged/aggregated proteins. There are two models for how aggregated proteins are segregating in a mother cell-biased fashion; one holds that asymmetric inheritance is a purely passive outcome of the aggregates' random but slow diffusion whereas the other model reasons that specific factors/organelles prevent free diffusion of aggregates into the daughter cell. In the present work, we tested whether the passive diffusion model or the factor-dependent model appear most relevant in explaining asymmetrical inheritance by quantifying traits predicted to affect inheritance by passive diffusion and identifying factors required for asymmetrical inheritance amongst essential genes interacting with SIR2; a gene shown previously to be required for mother-biased segregation. We show that passive diffusion of aggregates is not sufficient to establish mother-biased segregation and that ER to Golgi trafficking, in addition to the actin cytoskeleton, calmodulin, and the Myo2 motor protein, are key components restricting the inheritance of both heat stressed-induced aggregates and aggregates formed of the Huntington disease protein Htt103Q.

Vyšlo v časopise: Essential Genetic Interactors of Required for Spatial Sequestration and Asymmetrical Inheritance of Protein Aggregates. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004539
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004539

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