Showing papers by "Sina Ghaemmaghami published in 2016"
TL;DR: The described methodology significantly reduces the cost and complexity of temporally-resolved dynamic proteomic experiments and improves the precision of proteome-wide turnover data.
70 citations
TL;DR: The relative contribution of macroautophagy to basal proteome turnover is quantified by comparing protein half-lives between wild-type and autophagy-deficient fibroblasts to provide a global map of the selectivity of macroAutophagy in human cells.
65 citations
TL;DR: The methodology outlined in the study provides a global strategy for quantifying the selectivity of basal macroautophagy and indicates that in quiescent fibroblasts, macroautophile contributes to the basal turnover of a substantial fraction of the proteome.
Abstract: In eukaryotic cells, the macroautophagy pathway has been implicated in the degradation of long-lived proteins and damaged organelles. Although it has been demonstrated that macroautophagy can selectively degrade specific targets, its contribution to the basal turnover of cellular proteins had previously not been quantified on proteome-wide scales. In a recent study, we utilized dynamic proteomics to provide a global comparison of protein half-lives between wild-type and autophagy-deficient cells. Our results indicated that in quiescent fibroblasts, macroautophagy contributes to the basal turnover of a substantial fraction of the proteome. However, the contribution of macroautophagy to constitutive protein turnover is variable within the proteome. The methodology outlined in the study provides a global strategy for quantifying the selectivity of basal macroautophagy.
25 citations
TL;DR: These findings help to resolve the long-lasting debate regarding the signaling pathways of IAV-induced MMP9 expression and shed light on the molecular mechanisms underlying pulmonary capillary-alveolar leak syndrome that can occur during influenza infection.
Abstract: Investigation of influenza-A-virus (IAV)-infected lung proteomes will greatly promote our understanding on the virus-host crosstalk. Using a detergent-cocktail extraction and digestion procedure and a reproducible ion-current-based method, we performed the first comprehensive temporal analysis of mouse IAV infection. Mouse lung tissues at three time points post-inoculation were compared with controls (n = 4/group), and >1600 proteins were quantified without missing value in any animal. Significantly changed proteins were identified at 4 days (n = 144), 7 days (n = 695), and 10 days (n = 396) after infection, with low false altered protein rates (1.73–8.39%). Functional annotation revealed several key biological processes involved in the systemic host responses. Intriguingly, decreased levels of several cell junction proteins as well as increased levels of tissue metalloproteinase MMP9 were observed, reflecting the IAV-induced structural breakdown of lung epithelial barrier. Supporting evidence of MMP9 act...
10 citations