Our unit aims to elucidate how protein homeostasis (“proteostasis”) is 63regulated and maintained at the system level. In particular, we focus on the dynamics of nascent proteins to understand how the cellular proteome is shaped at the level of translation. To this end, we develop cutting-edge pro-teomic technologies to capture protein-specific information, including transla-tion, degradation, post-translational modifications, activity, and protein-protein interactions.In FY2022-2023, we developed technologies for global analysis of nascent polypeptides to understand translation control through the cytosolic or mito-chondrial ribosomes (Uchiyama et al. 2022 & Imami et al. 2023). Moreover, we have applied these technologies to monitor translation in vivo using model organisms such as mice, where we are focused on the brain. We are also sys-tematically profiling translational responses and co-translational modifications induced by environmental cues (stress, viruses, drugs, etc.) both in vitro and in vivo in order to understand the physiological function of translational control.Lipids regulate protein functions and proteostasis by binding covalently or non-covalently to proteins. Although the binding of hydrophilic metabolites to proteins has recently been investigated, no systematic and comprehensive study has examined the interaction between hydrophobic lipids and proteins. This is because their hydrophobic nature and low abundance make it particularly chal-lenging to analyze lipid-associated proteins and modifications. In corroboration with the metabolome group led by Dr. Makoto Arita, we are developing innova-tive proteomic techniques by integrating novel chemical probes, biochemical enrichment, and mass spectrometry-based informatics to comprehensively capture protein lipidation as well as the expression and activity of enzymes in-volved in the formation and regulation of lipid diversity (Tsumagari et al. 2023). In addition, we are developing a spatial proteomic method that should allow us to understand how lipids are distributed and regulated spatially in living organ-isms.Figure: Development and application of pSNAP (puromycin- and SILAC labeling-based nascent polypeptidome profiling) to mouse primary neuronal culturesThe principle of the enrichment of nascent polypeptide chains with the pSNAP is depicted. The pSNAP approach revealed differential nascent proteome profiles between 5 and 14 days in vitro (DIV) in mouse neuronal cultures.Recent Major PublicationsTsumagari K, Isobe Y, Ishihama Y, Seita J, Arita M, Imami K. Application of Liquid-Liquid Extraction for N-terminal Myristoylation Proteomics. Mol Cell Proteomics 12, 100677 (2023)Imami K, Selbach M, Ishihama Y. Monitoring mito-chondrial translation by pulse SILAC. J Biol Chem 299, 102865 (2023)Uchiyama J, Roy R, Wang DO, Morikawa K, Kawahara Y, Iwasaki M, Yoshino C, Mishima Y, Ishihama Y, Imami K. pSNAP: Proteome-wide analysis of elongating nascent polypeptide chains. iScience 25, 104516 (2022)Invited presentationsImami K, “Proteome homeostasis regulated through the interplay between protein synthesis and degradation” The 96th Annual Meeting of the Japanese Biochemical Society (Fukuoka, Japan) November 2023Imami K, “Protein N-terminal interactome” The 23rd Annual Meeting of the Protein Science Society of Japan (Nagoya, Japan) July 2023Imami K, “Biology of the extracellular vesicles from a proteomic perspective” 2023 Japanese Proteomics Soci-ety (Niigata, Japan) July 2023Proteome Homeostasis Research UnitUnit Leader: Koshi Imami
元のページ ../index.html#69