2026-07-13 ヒューストン大学
＜関連情報＞
- https://www.uh.edu/news-events/stories/2026/july/07132026-uh-copper-inbalances-neurodegenerative-diseases.php
- https://www.nature.com/articles/s41467-025-66283-w
細胞内銅濃度の上昇はCTR1の単量体化を誘導し、銅の取り込みを阻害する Elevated intracellular copper induces CTR1 monomerization and prevents copper uptake
Meng-Hsuan Wen,Huanhuan Chen,Guangjie Yan,Yuteng Zhang,Wenkai Chen,Martin V. Dokholyan,Jian Wang,Nikolay V. Dokholyan & Tai-Yen Chen
Nature Communications Published:12 December 2025
DOI:https://doi.org/10.1038/s41467-025-66283-w
Abstract
Copper is an essential element involved in various biochemical processes, such as mitochondrial energy production and antioxidant defense, but improper regulation can lead to cellular toxicity and disease. Copper Transporter 1 (CTR1) plays a key role in copper uptake and maintaining cellular copper homeostasis. Although CTR1 endocytosis was previously thought to reduce copper uptake when levels are high, it was unclear how rapid regulation is achieved. Using single-molecule localization microscopy and single-molecule neighbor density assays, we discover that elevated intracellular copper induces monomerization of the wild-type trimeric CTR1 prior to endocytosis, a response blocked in the endocytosis-deficient CTR1 (M150L) mutant. This monomerization correlates with a rapid halt in copper uptake. We propose that changes in CTR1 oligomerization state may regulate endocytosis and copper homeostasis.
