A gain-of-function TPC2 variant R210C increases affinity to PI(3,5)P2 and causes lysosome acidification and hypopigmentation

Qiaochu Wang; Zengge Wang; Yizhen Wang; Zhan Qi; Dayong Bai; Chentong Wang; Yuanying Chen; Wenjian Xu; Xili Zhu; Jaepyo Jeon; Jian Xiong; Chanjuan Hao; Michael Xi Zhu; Aihua Wei; Wei Li

doi:10.1038/s41467-023-35786-9

Nature Communications (Jan 2023)

A gain-of-function TPC2 variant R210C increases affinity to PI(3,5)P2 and causes lysosome acidification and hypopigmentation

Qiaochu Wang,
Zengge Wang,
Yizhen Wang,
Zhan Qi,
Dayong Bai,
Chentong Wang,
Yuanying Chen,
Wenjian Xu,
Xili Zhu,
Jaepyo Jeon,
Jian Xiong,
Chanjuan Hao,
Michael Xi Zhu,
Aihua Wei,
Wei Li

Affiliations

Qiaochu Wang: Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute
Zengge Wang: Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute
Yizhen Wang: Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute
Zhan Qi: Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute
Dayong Bai: Department of Ophthalmology, Beijing Children’s Hospital, Capital Medical University; National Center for Children’s Health
Chentong Wang: Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute
Yuanying Chen: Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute
Wenjian Xu: Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute
Xili Zhu: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences
Jaepyo Jeon: Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston
Jian Xiong: Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston
Chanjuan Hao: Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute
Michael Xi Zhu: Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston
Aihua Wei: Department of Dermatology, Tongren Hospital, Capital Medical University
Wei Li: Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute

DOI: https://doi.org/10.1038/s41467-023-35786-9
Journal volume & issue: Vol. 14, no. 1
pp. 1 – 16

Abstract

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TPC2 is an important organellar Na+/Ca2+ release channel which regulates function of lysosomes and lysosome-related organelles. Here, Wang et al. demonstrate that a gain-of-function mutation (R210C) in TPC2 leads to hypopigmentaion, enlarged endolysosomes, enhanced lysosomal Ca2+ release and hyper-acidification.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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