
Faculty, Staff and Student Publications
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
DOI
10.1038/s41467-023-35786-9
PMID
36641477
PMCID
PMC9840614
PubMedCentral® Posted Date
January 2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes