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경북대학교, 오가시스(주)

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Autophagy, Oct 30 2024, | https://doi.org/10.1080/15548627.2024.2421695 Deciphering melanophagy: role of the PTK2-ITCH-MLANA-OPTN cascade on melanophagy in melanocytes

Na Yeon Park ^{1 †}, Doo Sin Jo ^{2 †}, Hyun Jun Park ¹, Ji-Eun Bae ³, Yong Hwan Kim ¹, Joon Bum Kim ¹, Ha Jung Lee^{1 2}, Sung Hyun Kim ¹, Hyunjung Choi ⁴, Hyun-Shik Lee ^{1 3}, Tamotsu Yoshimori ⁵, Dong-Seok Lee ^{1 6}, Jin-A Lee ⁷, Pansoo Kim ², Dong-Hyung Cho ^{1 2 6 *}

¹School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.

²ORGASIS Corp, Suwon, Gyeonggi-do, Republic of Korea.

³KNU G-LAMP Project Group, KNU Institute of Basic Sciences, Kyungpook National University, Daegu, Republic of Korea.

⁴R&D Unit, AmorePacific Corporation, Yongin, Gyeonggi-do, Republic of Korea.

⁵Department of Genetics, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.

⁶Organelle Institute, KNU, Daegu, Republic of Korea.

⁷Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University, Daejeon, Republic of Korea.

^†These authors contributed equally
^*Corresponding author: correspondence to Dong-Hyung Cho

Abstract

Melanosomes play a pivotal role in skin color and photoprotection. In contrast to the well-elucidated pathway of melanosome biogenesis, the process of melanosome degradation, referred to as melanophagy, is largely unexplored. Previously, we discovered that 3,4,5-trimethoxycinnamate thymol ester (TCTE) effectively inhibits skin pigmentation by activating melanophagy. In this study, we discovered a new regulatory signaling cascade that controls melanophagy in TCTE-treated melanocytes. ITCH (itchy E3 ubiquitin protein ligase) facilitates ubiquitination of the melanosome membrane protein MLANA (melan-A) during TCTE-induced melanophagy. This ubiquitinated MLANA is then recognized by an autophagy receptor protein, OPTN (optineurin). Additionally, a phospho-kinase antibody array revealed that TCTE activates PTK2 (protein tyrosine kinase 2), which phosphorylates ITCH, enhancing the ubiquitination of MLANA. Furthermore, inhibition of either PTK2 or ITCH disrupts the ubiquitination of MLANA and the MLANA-OPTN interaction in TCTE-treated cells. Taken together, our findings highlight the critical role of the PTK2-ITCH-MLANA-OPTN cascade in orchestrating melanophagy progression.

논문정보

형식Research article
게재일2024년 10월 (BRIC 등록일 2024-11-01)
연구진국내(교신)+국외 연구진
분야 생명과학 > 세포생물학

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