Principal Investigator: Prof. Bruno Reversade
Poster Presenter: Aljohara Alotaibi
Lab: Laboratory of human genetics and therapeutics
The protein encoded by TAPT1 exists in all eukaryotic cells. Together with its direct interacting partner SUCO, it forms a stoichiometric protein complex situated in the ER/Golgi apparatus (Baldwin et al, 1996, 2000; Jonikas et al, 2009; Symoens et al, 2015; LaMonte et al, 2016, 2020; Zhang et al, 2017a, 2017b). Despite its universal and constitutive expression, the true molecular function of these membrane-spanning proteins is poorly understood. Previously we identified a deep intronic mutation in TAPT1 (c.1237-52 G>A) which leads to a protein-null allele in patients with a progeroid Osteogenesis Imperfecta (OI). Transcriptomic analysis using RNA-Seq and SI-NET-Seq revealed that collagen and ECM-related pathway genes are differentially regulated in patient knockout fibroblast (Nabavizadeh et al., 2023). This cellular phenotype was also validated in cells from another patient carrying a homozygous missense p. Leu108Trp (Etich et al., 2023) where abnormal collagen fiber formation was seen. We hypothesize that TAPT1/SUCO may function as a chaperone of client proteins bearing a specific post-translational modification (PTM) which is essential for collagen synthesis and/or assembly. To elucidate the evolutionarily-conserved function of this unique protein complex, we will utilize integrated metabolomic and proteomic approaches including cross-linking mass spectrometry (XL-MS) and TurboID proximity-labeling on patient-derived and yeast knockout cells.