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Anoctamin 6 is localized in the primary cilium of renal tubular cells and is involved in apoptosis-dependent cyst lumen formation.

Forschbach V, Goppelt-Struebe M, Kunzelmann K, Schreiber R, Piedagnel R, Kraus A, Eckardt KU, Buchholz B - Cell Death Dis (2015)

Bottom Line: 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.These data identify ANO6 as a cilium-associated protein and suggest its functional relevance in cyst formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nuernberg, 91054 Erlangen, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

ANO6 is localized in the primary cilia of renal tubule cells and strongly expressed in apoptotic cyst epithelial cells in vivo. Sections of human polycystic kidneys were stained for acetylated tubulin (a and c) and ANO6 (b and d); (e and i) brightfield view of sections of human polycystic kidneys are shown, further stained with DAPI (f and j), the apoptotic marker BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3; g and k) and ANO6 (h and l). Arrows point at cilia
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fig7: ANO6 is localized in the primary cilia of renal tubule cells and strongly expressed in apoptotic cyst epithelial cells in vivo. Sections of human polycystic kidneys were stained for acetylated tubulin (a and c) and ANO6 (b and d); (e and i) brightfield view of sections of human polycystic kidneys are shown, further stained with DAPI (f and j), the apoptotic marker BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3; g and k) and ANO6 (h and l). Arrows point at cilia

Mentions: To determine the relevance of these findings for polycystic kidney disease in humans, we analyzed sections of human polycystic kidneys. In polycystic kidneys, increased apoptosis is a key feature of the cyst epithelium and highly correlates with the degree of cyst formation.24 ANO6 could be detected in human cyst-lining cells and—in line with the in vitro data—colocalized with the ciliary marker acetylated tubulin (Figures 7a–d). In addition, ANO6 was highly expressed in rounded apoptotic epithelial cells characterized by strong expression of the pro-apoptotic protein BNIP3 (Figures 7e–l), supporting the hypothesis of a functional role of ANO6 in apoptosis of cyst-lining epithelial cells.


Anoctamin 6 is localized in the primary cilium of renal tubular cells and is involved in apoptosis-dependent cyst lumen formation.

Forschbach V, Goppelt-Struebe M, Kunzelmann K, Schreiber R, Piedagnel R, Kraus A, Eckardt KU, Buchholz B - Cell Death Dis (2015)

ANO6 is localized in the primary cilia of renal tubule cells and strongly expressed in apoptotic cyst epithelial cells in vivo. Sections of human polycystic kidneys were stained for acetylated tubulin (a and c) and ANO6 (b and d); (e and i) brightfield view of sections of human polycystic kidneys are shown, further stained with DAPI (f and j), the apoptotic marker BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3; g and k) and ANO6 (h and l). Arrows point at cilia
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4632301&req=5

fig7: ANO6 is localized in the primary cilia of renal tubule cells and strongly expressed in apoptotic cyst epithelial cells in vivo. Sections of human polycystic kidneys were stained for acetylated tubulin (a and c) and ANO6 (b and d); (e and i) brightfield view of sections of human polycystic kidneys are shown, further stained with DAPI (f and j), the apoptotic marker BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3; g and k) and ANO6 (h and l). Arrows point at cilia
Mentions: To determine the relevance of these findings for polycystic kidney disease in humans, we analyzed sections of human polycystic kidneys. In polycystic kidneys, increased apoptosis is a key feature of the cyst epithelium and highly correlates with the degree of cyst formation.24 ANO6 could be detected in human cyst-lining cells and—in line with the in vitro data—colocalized with the ciliary marker acetylated tubulin (Figures 7a–d). In addition, ANO6 was highly expressed in rounded apoptotic epithelial cells characterized by strong expression of the pro-apoptotic protein BNIP3 (Figures 7e–l), supporting the hypothesis of a functional role of ANO6 in apoptosis of cyst-lining epithelial cells.

Bottom Line: 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.These data identify ANO6 as a cilium-associated protein and suggest its functional relevance in cyst formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nuernberg, 91054 Erlangen, Germany.

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.

No MeSH data available.


Related in: MedlinePlus