title: Identification of Sidt2 as a lysosomal cation-conducting protein.
abstract: 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 HEK293 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.
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beck
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fecher-Trost
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Wolske
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, Germany.
authors.forename: Stephan E
authors.initials: SE
authors.lastname: Philipp
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, Germany.
authors.forename: Veit
authors.initials: V
authors.lastname: Flockerzi
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wissenbach
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D000588:Amines; D000818:Animals; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism; D048430:Cell Shape; D048429:Cell Size; D004553:Electric Conductivity; D019143:Evolution, Molecular; D057809:HEK293 Cells; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D033704:Nucleotide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D014162:Transfection; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D000588:Amines; D002412:Cations; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D033704:Nucleotide Transport Proteins; D012964:Sodium; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C493330:Red DND-99; C000613088:SIDT2 protein, human; C554947:Sidt2 protein, mouse
keywords: Sidt2; counter ion flux; ion channel