Cu-dependent CTR1 oligomerization and Cu-uptake regulation

Copper enters cells through pores formed by trimeric Human copper transporter 1 (hCTR1). Elevated Cu induces clathrin-dependent endocytosis of hCTR1 and decreases the hCTR1 surface abundance by half. However, it remains unclear how cells minimize the Cu-uptake activity of the remaining surface hCTR1. This study examined the oligomeric states of hCTR1 complexes in fixed COS7 cells using super-resolution localization microscopy and single-molecule oligomeric state quantification assay. We found that the hCTR1 on the plasma membrane exists dominantly in the trimeric form (~80%) under basal conditions and shifts to monomeric states (~50%) under Cu stressed conditions. This finding suggests cells may further modulate the oligomer distributions of the surface hCTR1 to reduce cellular Cu-uptake and provide insight into the hCTR1 transport mechanism.

Tai-Yen earned his B.S. (2002) and M.S. (2004) in Chemistry from National Tsing Hua University and a Ph.D. (2010) from Texas A&M University before pursuing a postdoctoral associate (2011-2016) at Cornell University. Tai-Yen started his independent career as an assistant professor of the Department of Chemistry at the University of Houston in 2016. His research focuses on the metal homeostasis in healthy and diseased neurons using single-molecule techniques. In particular, his group is interested in the dynamics and mechanisms of protein machinery involved in Cu trafficking within/between neurons. His research goal is to understand how metals affect neuronal signaling and cause neurodegenerative diseases. His work has been recognized with the Maximizing Investigators' Research Award for Early Stage Investigators and a Robert A. Welch Foundation grant. Besides research, Tai-Yen enjoys and enthusiastically participates in multiple educational activities. In recognition of his classroom teaching and laboratory mentorship, Tai-Yen received the College's highly competitive John C. Butler Excellence in Teaching Award in 2021.