4.5 Article

Proteome-wide abundance profiling of yeast deletion strains for GET pathway members using sample multiplexing

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PROTEOMICS
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WILEY
DOI: 10.1002/pmic.202300303

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FAIMS; GET pathway; isobaric tagging; RTS-MS3; TMTpro

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The study investigates the impact of dysfunction in the GET pathway on protein abundance in yeast deletion strains. The findings reveal differential abundance of certain proteins in the deletion strains, some of which are membrane-associated, while the abundance of many tail-anchored proteins remains unchanged. This study provides valuable insights into the roles of GET genes and alternative pathways that maintain cellular function despite disruption of the GET pathway.
The GET pathway is associated with post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (ER) in yeast, as well as other eukaryotes. Moreover, dysfunction of the GET pathway has been associated with various pathological conditions (i.e., neurodegenerative disorders, cardiovascular ailments, and protein misfolding diseases). In this study, we used yeast deletion strains of Get complex members (specifically, Get1, Get2, Get3, Get4, and Get5) coupled with sample multiplexing-based quantitative mass spectrometry to profile protein abundance on a proteome-wide scale across the five individual deletion strains. Our dataset consists of over 4500 proteins, which corresponds to >75% of the yeast proteome. The data reveal several dozen proteins that are differentially abundant in one or more deletion strains, some of which are membrane-associated, yet the abundance of many TA proteins remained unchanged. This study provides valuable insights into the roles of these Get genes, and the potential for alternative pathways which help maintain cellular function despite the disruption of the GET pathway.

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