The Ca2+-activated Cl- channel ANO1/TMEM16A regulates primary ciliogenesis
Chelsey Chandler Ruppersburg1, H Criss Hartzell2
1Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322.
Molecular Biology of the Cell
|April 4, 2014
Summary
The Ca(2+)-activated Cl(-) channel anoctamin-1 (ANO1/TMEM16A) is essential for primary cilium formation. This channel organizes into a structure called "the nimbus," crucial for early ciliogenesis.
Area of Science:
- Cell Biology
- Molecular Biology
- Biophysics
Background:
- Primary cilia are critical for cellular morphogenesis and sensory transduction.
- Ion channels are vital for sensory transduction, but their role in primary cilia is largely unknown, except for TRPP2.
Purpose of the Study:
- To investigate the role of the Ca(2+)-activated Cl(-) channel anoctamin-1 (ANO1/TMEM16A) in primary cilia.
- To elucidate the function of ANO1/TMEM16A in ciliogenesis and its localization within the primary cilium.
Main Methods:
- Pharmacological inhibition and short hairpin RNA (shRNA) knockdown of ANO1/TMEM16A.
- Immunofluorescence microscopy to visualize protein localization and cellular structures.
- Analysis of ciliogenesis and the formation of the "nimbus" structure.
Main Results:
- ANO1/TMEM16A localizes to the primary cilium and is required for ciliogenesis.
- ANO1/TMEM16A forms a torus-shaped structure called "the nimbus" before ciliogenesis.
- The nimbus is enriched with ciliogenesis proteins (Cdc42, Arl13b, Sec6) and excludes F-actin, coinciding with acetylated microtubules.
Conclusions:
- The nimbus acts as a scaffold for organizing ciliary components during early ciliogenesis.
- Chloride transport by ANO1/TMEM16A is necessary for the formation and maintenance of primary cilia.
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