The Ca2+-activated Cl- channel ANO1/TMEM16A regulates primary ciliogenesis.
Many cells possess a single, nonmotile, primary cilium highly enriched in receptors and sensory transduction machinery that plays crucial roles in cellular morphogenesis. Although sensory transduction requires ion channels, relatively little is known about ion channels in the primary cilium (with the exception of TRPP2). Here we show that the Ca(2+)-activated Cl ((-)) channel anoctamin-1 (ANO1/TMEM16A) is located in the primary cilium and that blocking its channel function pharmacologically or knocking it down with short hairpin RNA interferes with ciliogenesis. Before ciliogenesis, the channel becomes organized into a torus-shaped structure ("the nimbus") enriched in proteins required for ciliogenesis, including the small GTPases Cdc42 and Arl13b and the exocyst complex component Sec6. The nimbus excludes F-actin and coincides with a ring of acetylated microtubules. The nimbus appears to form before, or independent of, apical docking of the mother centriole. Our data support a model in which the nimbus provides a scaffold for staging of ciliary components for assembly very early in ciliogenesis and chloride transport by ANO1/TMEM16A is required for the genesis or maintenance of primary cilia.
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322.
Chelsey Chandler
CC
Ruppersburg
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322 criss.hartzell@emory.edu.
H Criss
HC
Hartzell
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D000075369:Anoctamin-1; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D016764:Cell Polarity; D018385:Centrosome / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D015640:Ion Channel Gating; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D038081:Organogenesis; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats
C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; D018118:Chloride Channels; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; C071058:moesin; D002118:Calcium