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Vesicular Transport Mediated by Endoplasmic Reticulum Stress Sensor BBF2H7 Orchestrates Melanin Production During
Giang Huy Phan1, Kenshiro Fujise1, Kazunori Imaizumi2,3
1Department of Frontier Science and Interdisciplinary Research, Faculty of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8640, Ishikawa, Japan.
International Journal of Molecular Sciences
|January 10, 2026
Summary
The BBF2H7-Sec23a pathway is crucial for transporting Tyrosinase, essential for melanin production, from the ER to melanosomes. This pathway is vital for skin pigmentation and UV protection.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Melanin pigment synthesis in melanocytes protects against UV radiation.
- Tyrosinase is a key enzyme in melanogenesis, catalyzing melanin production.
- Tyrosinase transport from the ER to melanosomes is critical for melanogenesis.
Purpose of the Study:
- To investigate the role of BBF2H7 in Tyrosinase transport and melanogenesis.
- To elucidate the molecular mechanism linking ER stress to Tyrosinase transport.
- To identify potential therapeutic targets for pigmentation disorders.
Main Methods:
- Studied the activation of BBF2H7 by ER stress induced by Tyrosinase synthesis.
- Investigated the effect of BBF2H7 on Sec23a expression and COPII-mediated transport.
- Analyzed Tyrosinase transport and melanin production in Bbf2h7-deficient melanocytes.
Main Results:
- Mild ER stress from Tyrosinase synthesis activates BBF2H7.
- Activated BBF2H7 enhances anterograde transport by inducing Sec23a expression.
- Loss of BBF2H7 impairs Tyrosinase transport, reducing melanin synthesis.
Conclusions:
- The BBF2H7-Sec23a axis is essential for ER-to-melanosome Tyrosinase transport.
- This pathway is critical for maintaining melanin synthesis and skin pigmentation.
- The BBF2H7-Sec23a pathway represents a potential therapeutic target for pigmentation disorders.
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