Dr. Tai-Yen Chen

Seminar Details

Host: Dr. Vishal Gohil

Time: 4:00pm-5:00pm

Location: BICH Rm 108

Download Seminar Flyer

Seminar Abstract

Copper is essential for cellular physiology, but its reactivity requires tight control over uptake, distribution, and protein metalation. This seminar will examine how copper availability regulates protein assembly and cellular fate at two points in copper biology. First, I will present our work on copper transporter 1 (CTR1), the major high-affinity pathway for cellular copper uptake. Using single-molecule localization microscopy and neighbor-density analysis, we resolved CTR1 oligomeric populations and trafficking in intact cells. Elevated copper shifted wild-type CTR1 from a predominantly trimeric population toward monomers before internalization, with de-oligomerized CTR1 enriched at Rab5-positive early endocytic sites. The endocytosis-deficient M150L variant failed to undergo this transition. The oligomeric shift coincided with rapid cessation of copper uptake, supporting a two-stage model in which structural remodeling suppresses transport before sustained removal from the cell surface. I will then discuss preliminary studies of superoxide dismutase 1 (SOD1), whose maturation depends on copper delivery and the copper chaperone CCS. Copper depletion revealed a reversible, low-activity SOD1 species that migrates below the native dimer, is enriched in the nucleus, and is promoted by CCS loss. Its native mobility and thiol sensitivity are consistent with a monomer-like state, although absolute stoichiometry remains unresolved. Live-cell measurements further show nuclear redistribution and an altered cytosolic proximity readout under copper depletion. Together, these studies suggest that copper-controlled protein assembly may regulate transport, localization, and function across distinct stages of cellular copper homeostasis. These complementary measurements connect nanoscale assembly changes to cellular responses while defining testable structural and mechanistic questions.