2024/08/02 by Alejandro N. Rondón-Ortiz, Lushuang Zhang, Peter E.A. Ash +7 · 1 voice
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Cellular transport and secretion #Endoplasmic Reticulum Stress and Disease #Genetic Neurodegenerative Diseases
paper · pdf · doi:10.1016/j.jbc.2024.107621
openalex publication_date 2024/08/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Sequestosome1 (SQSTM1) is an autophagy receptor that mediates the degradation of intracellular cargo, including protein aggregates, through multiple protein interactions. These interactions form the SQSTM1 protein network, and these interactions are mediated by SQSTM1 functional interaction domains, which include LIR, PB1, UBA, and KIR. Technological advances in cell biology continue to expand our knowledge of the SQSTM1 protein network and the relationship between the actions of the SQSTM1 protein network in cellular physiology and disease states. Here we apply proximity profile labeling to investigate the SQSTM1 protein interaction network by fusing TurboID with the human protein SQSTM1 (TurboID::SQSTM1). This chimeric protein displayed well-established SQSTM1 features including production of SQSTM1 intracellular bodies, binding to known SQSTM1 interacting partners, and capture of novel SQSTM1 protein interactors. Strikingly, aggregated tau protein altered the protein interaction network of SQSTM1 to include many stress-associated proteins. We demonstrate the importance of the PB1 and/or UBA domains for binding network members, including the K18 domain of tau. Overall, our work reveals the dynamic landscape of the SQSTM1 protein network and offers a resource to study SQSTM1 function in cellular physiology and disease state.