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Identification of Sidt2 as a lysosomal cation‐conducting protein
Author(s) -
Beck Andreas,
FecherTrost Claudia,
Wolske Karin,
Philipp Stephan E.,
Flockerzi Veit,
Wissenbach Ulrich
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12528
Subject(s) - identification (biology) , chemistry , biochemistry , microbiology and biotechnology , biology , botany
A screen to identify lysosomal‐expressed ion channels led to the discovery of the human Sidt2 protein. Sidt2 is expressed within lysosomal organelles but as a result of heterologous overexpression the protein is also detectable within the plasma membrane of human embryonic kidney cells. The overexpressed protein leads to cell depolarization upon sodium addition. Accordingly in whole‐cell patch clamp experiments a spontaneous noninactivating monovalent cation current can be detected in Sidt2‐overexpressing cells. Strong overexpression of Sidt2 in HEK 293 cells is attended by a significant reduction/loss of detectable lysosomes, indicating that the overexpressed protein leads to lysosomal dysfunction, a hallmark of Alzheimer's disease. Sidt2 is located on chromosome 11q23, a locus repeatedly found by chromosomal mapping of Alzheimer's disease‐related genes.