title: Anoctamin 6 is localized in the primary cilium of renal tubular cells and is involved in apoptosis-dependent cyst lumen formation.
abstract: Primary cilia are antenna-like structures projected from the apical surface of various mammalian cells including renal tubular cells. Functional or structural defects of the cilium lead to systemic disorders comprising polycystic kidneys as a key feature. Here we show that anoctamin 6 (ANO6), a member of the anoctamin chloride channel family, is localized in the primary cilium of renal epithelial cells in vitro and in vivo. ANO6 was not essential for cilia formation and had no effect on in vitro cyst expansion. However, knockdown of ANO6 impaired cyst lumen formation of MDCK cells in three-dimensional culture. In the absence of ANO6, apoptosis was reduced and epithelial cells were incompletely removed from the center of cell aggregates, which form in the early phase of cystogenesis. In line with these data, we show that ANO6 is highly expressed in apoptotic cyst epithelial cells of human polycystic kidneys. These data identify ANO6 as a cilium-associated protein and suggest its functional relevance in cyst formation.
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nuernberg, 91054 Erlangen, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Forschbach
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nuernberg, 91054 Erlangen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Goppelt-Struebe
authors.affiliation: Department of Physiology, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Kunzelmann
authors.affiliation: Department of Physiology, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schreiber
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155, F-75005 Paris, France.|INSERM, UMR_S 1155, F-75005 Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Piedagnel
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nuernberg, 91054 Erlangen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kraus
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nuernberg, 91054 Erlangen, Germany.
authors.forename: K-U
authors.initials: KU
authors.lastname: Eckardt
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nuernberg, 91054 Erlangen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Buchholz
mesh_terms: D000075368:Anoctamins; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism*; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D007690:Polycystic Kidney Diseases / Q000378:metabolism*; D021381:Protein Transport
chemical_list: C555078:ANO6 protein, human; D000075368:Anoctamins; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids