Cereblon-mediated TRPC1 degradation regulates Ca2+ influx in the heart

Authors

• Nammi Park, Inje University, South Korea
• Jubert Marquez, De La Salle University, Manila
• Tuyet Anh Thi Nguyen, Inje University, South Korea
• Jessa Flores, Inje University, South Korea
• Maria Victoria Faith Garcia, Inje University, South Korea
• Ippei Shimizu, National Cerebral and Cardiovascular Center
• Joohyun Nam, Dongguk University College of Medicine
• Bernd Nilius, KU Leuven
• Hyoung Kyu Kim, Inje University, South Korea
• Jin Han, Inje University, South Korea

College

College of Science

Department/Unit

Biology

Document Type

Article

Source Title

Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease

Volume

1870

Publication Date

2024

Abstract

• This study investigated how cereblon (CRBN), a substrate receptor of the E3 ubiquitin ligase complex that selectively degrades ion channels, targets cardiac transient receptor potential channel 1 (TRPC1).
• Physiologically, CRBN ablation upregulated TRPC1 expression.
• Mechanistically, the CRBN Lon domain directly interacts with the C- and N-terminals of TRPC1.
• Increasing CRBN levels enhanced TRPC1 ubiquitination and proteasomal degradation.
• TRPC1 overexpression in HEK293-CRBN KO cells enhanced TRPC1 current density and Ca2+ transients.
• Pathologically, cardiac TRPC1 expression in CRBN-deficient mice was increased during ex vivo ischemic/reperfusion.
• Targeting the CRBN-TRPC1 axis may serve as a novel therapeutic approach to address cardiac disease.

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Recommended Citation

Park, N., Marquez, J., Nguyen, T. T., Flores, J., Garcia, M., Shimizu, I., Nam, J., Nilius, B., Kim, H., & Han, J. (2024). Cereblon-mediated TRPC1 degradation regulates Ca2+ influx in the heart. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1870 Retrieved from https://animorepository.dlsu.edu.ph/faculty_research/15416

Disciplines

Cardiovascular Diseases

Keywords

Biological response modifiers; Calcium; Ischemia; Reperfusion (Physiology)

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