# A Role for the Calcium activated Chloride Channel TMEM16a in Primary Ciliogenesis

> **NIH NIH F31** · EMORY UNIVERSITY · 2021 · $46,036

## Abstract

PROJECT SUMMARY
The primary cilium, an apical cellular appendage akin to a cellular antenna, is involved in a variety of physiological
processes including development, proliferation, and cell survival. Mutations in many genes linked to ciliary
proteins cause a family of human diseases termed ciliopathies which include Joubert Syndrome and Bardet-
Biedl syndrome. Evidencing the ubiquitous function of the primary cilium, these diseases present diverse clinical
phenotypes affecting many of the body’s organ systems. As fundamental signaling hubs with distinct protein and
lipid compositions relative to the rest of the cell, primary cilia are highly regulated in both their formation and
function. Ion channels represent a unique class of proteins which regulate signaling events in many cellular
processes, but are only beginning to be understood and appreciated in the context of the cilium. We are using a
combination of electrophysiology and cell imaging to study the role of the calcium activated chloride channel
ANO1 in regulating primary ciliogenesis and ciliary signaling. We recently found that Ano1 knock out results in
fewer and shorter cilia compared to cells expressing ANO1. Furthermore, knock out of Ano1 in mice results in
neonatal lethality due to tissue malformation mirroring classical ciliopathy hallmarks. We also recently
characterized a novel cellular structure, the nimbus, which contains ANO1 and appears spatio-temporally related
to ciliogenesis. We will test the hypothesis that ANO1 plays a role in regulating cilium formation and function.
First, we will characterize the localization and activity of ANO1 during ciliogenesis. These experiments when
during ciliogenesis ANO1 activity is important, and what step(s) of ciliogenesis ANO1 regulates. Finally, we will
quantify ciliary signaling outputs in the presence and absence of ANO1. This work will allow us to elucidate the
role of ANO1 in primary ciliogenesis, the functional consequence of loss of ANO1, and provide insight into
primary cilium ion channel biology overall. Understanding the molecular pathways will provide valuable insights
into the study of calcium activated chloride channels, and ion channels in the primary cilium. This fundamental
knowledge can then be applied to primary cilia in the context of organismal development and ciliopathies and
may provide new insight into pathways and targets for the treatment of these diseases.

## Key facts

- **NIH application ID:** 10127680
- **Project number:** 5F31HD096815-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Skylar Fisher
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127680

## Citation

> US National Institutes of Health, RePORTER application 10127680, A Role for the Calcium activated Chloride Channel TMEM16a in Primary Ciliogenesis (5F31HD096815-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10127680. Licensed CC0.

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