# Regulation and functional characterization of ciliary calcium signaling

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $355,300

## Abstract

PROJECT SUMMARY
How can the second messenger Ca2+ regulate a plethora of signaling processes as diverse as fertilization,
proliferation, development, learning and memory, contraction and secretion? Compartmentalized Calcium
signaling is a fundamental signaling principle by which Ca2+ ions exert their stimulatory function locally in a
precisely controlled spatial and temporal manner. Changes in local Ca2+ concentration within the cell are
regulated through Ca2+ entry across the plasma membrane to generate “signaling hot spots” or by releasing
Ca2+ from intracellular stores such as endoplasmic reticulum (ER), mitochondria or endosomes. Changes in
Ca2+ concentration are “sensed” by Ca2+ binding proteins which relay the information into a signaling output.
The primary cilium is a microtubule based organelle extending from the apical plasma membrane and shaped
like an antenna. Primary cilia are enriched in a specific subset of calcium permeating ion channels called
polycystins (PC1 and PC2). While the Ca2+ signaling field has made seminal progress in understanding the
molecular principles of compartmentalized Ca2+ signaling in organelles such as ER and endosomes, we are
still lacking a functional understanding of the primary cilium as a Ca2+ signaling organelle. Mutations in
polycystin ion channels result in a variety of human diseases, ranging from congenital heart disease and
laterality defects to cyst formation in multiple organs (liver, kidney and pancreas). Ca2+ is likely to function as a
critical second messenger within primary cilia in all of these organs, but the functional consequences of ciliary
calcium signaling remain mysterious and so do the mechanisms through which ciliary ion channels are
regulated. The central goal of this project is to understand how the cilia ion channels PC1 and PC2 regulate
ciliary Ca2+ levels and to determine the cell biological function of compartmentalized ciliary Ca2+ signaling.
There are three specific aims. The first aim is to determine how PC1/PC2 channel activity affects ciliary Ca2+
concentration. The second aim tests the hypothesis that changes in ciliary calcium concentration regulate the
permeability for proteins of the transition zone, a diffusion barrier at the base of the primary cilium. The third
aim determines how the N-terminus of PC1, a 3000 amino acid long fragment decorated with multiple cell
adhesion domains, regulates PC1/PC2 ion channel activity. The applicants' preliminary observations include
novel unpublished methods to r‐ecord PC1/PC2 channel activity and to dynamically regulate ciliary Ca2+
concentration. Completion of this project will be a critical first step in understanding the cell biological function
ciliary calcium signaling. Our long term goal is to understand how dysregulation of ciliary Ca2+ dynamics cause
human ciliopathies.

## Key facts

- **NIH application ID:** 10245017
- **Project number:** 5R01GM130908-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Markus G Delling
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $355,300
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10245017

## Citation

> US National Institutes of Health, RePORTER application 10245017, Regulation and functional characterization of ciliary calcium signaling (5R01GM130908-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10245017. Licensed CC0.

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