A Gain-of-function TPC2 Variant R210c Increases Affinity to PI(3,5)P

Authors

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

Publication Date

1-14-2023

Journal

Nature Communications

Abstract

Albinism is a group of inherited disorders mainly affecting skin, hair and eyes. Here we identify a de novo point mutation, p.R210C, in the TPCN2 gene which encodes Two Pore Channel 2 (TPC2) from a patient with albinism. TPC2 is an endolysosome and melanosome localized non-selective cation channel involved in regulating pigment production. Through inside-out recording of plasma membrane targeted TPC2 and direct recording of enlarged endolysosomal vacuoles, we reveal that the R210C mutant displays constitutive channel activation and markedly increased affinity to PI(3,5)P

Keywords

Animals, Mice, Albinism, Fibroblasts, Gain of Function Mutation, Hydrogen-Ion Concentration, Lysosomes, Calcium Channels