title: Cellular defects by deletion of ANO10 are due to deregulated local calcium signaling.
abstract: TMEM16K (ANO10) belongs to a family of ion channels and phospholipid scramblases. Mutations in ANO10 cause neurological and immunological defects, and abrogated ion transport. Here we show that Ano10 knockout in epithelial cells leads to defective ion transport, attenuated volume regulation and deranged Ca2+signaling. Intestinal epithelial cells from Ano10 null mice are reduced in size and demonstrate an almost abolished spontaneous and TNFα-induced apoptosis. Similar defects were found in mouse peritoneal Ano10 null macrophages and in human THP1 macrophages with reduced ANO10 expression. A cell cycle dependent colocalization of Ano10 with acetylated tubulin, centrioles, and a submembranous tubulin containing compartment was observed in Fisher rat thyroid cells. Axs, the Drosophila ortholog of ANO10 is known for its role in mitotic spindle formation and association with the endoplasmic reticulum and Ca2+signaling. We therefore propose that mutations in ANO10 cause cellular defects and genetic disorders through deranged local Ca2+signaling.
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany.
authors.forename: Podchanart
authors.initials: P
authors.lastname: Wanitchakool
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany.
authors.forename: Jiraporn
authors.initials: J
authors.lastname: Ousingsawat
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany.
authors.forename: Lalida
authors.initials: L
authors.lastname: Sirianant
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany.
authors.forename: Inês
authors.initials: I
authors.lastname: Cabrita
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Faria
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schreiber
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany. Electronic address: karl.kunzelmann@ur.de.
authors.forename: Karl
authors.initials: K
authors.lastname: Kunzelmann
mesh_terms: D000818:Animals; D000075368:Anoctamins / Q000172:deficiency / Q000378:metabolism*; D017209:Apoptosis; D020013:Calcium Signaling; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D048429:Cell Size; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D057809:HEK293 Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D018345:Mice, Knockout; D021381:Protein Transport; D051381:Rats
chemical_list: D000075368:Anoctamins; D053148:Caspase 3
keywords: ANO10; Anoctamin 10; Apoptosis; Ca(2+) signaling; Ion channels; Jejunum; Macrophages; TMEM16K