# A comprehensive map of polycystin channel regulation and its implications in polycystic kidney disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $635,357

## Abstract

PROJECT SUMMARY
Ion channels control such diverse processes as fertilization, proliferation, development, learning and memory.
Ion channels are multispan transmembrane proteins that transport ~106 to 107 ions per second across
membranes. Precise spatial and temporal regulation of ionic flux is the fundamental principle by which ion
channels control such a diverse array of signaling modalities. Spatial regulation is achieved by targeting channels
to subcellular compartments ensheathed in membranes such as the endoplasmic reticulum (ER) or endosomes,
whereas temporal regulation by specific signals controlling opening and closing of channels. The primary cilium
is an antenna-shaped protrusion from the apical plasma membrane and are enriched in a specific subset of ion
channels called polycystins. Mutations in polycystins cause Autosomal Dominant Polycytsic Kidney Disease
(ADPKD), which manifests in cyst formation in kidney and other organs, such as liver and pancreas. The
molecular mechanisms by which polycystin channels are spatially and temporally regulated and thus contribute
to ciliary signaling cascades still remain poorly understood. The central goal of this project is to understand the
fundamental mechanisms at the molecular and cellular level by which polycystin channels are activated in
primary cilia. There are three specific aims. The first aim defines the molecular motifs in PC1 and PC2 underlying
the temporal regulation of the ciliary polycystin channel complex. The second aims defines the local regulation
of polycystins by ciliary calcium levels. The third aim determine the physiological role of ciliary lipids in restricting
polycystin activity to primary cilia. This proposal includes preliminary observations of two applicants with
complementary expertise on polycystin channel function. Completion of this project will be a critical step towards
understanding the fundamental principles of polycystin channel signaling within primary cilia. Our long‐term goal
is to understand how dysregulation of polycystin channels causes ADPKD.

## Key facts

- **NIH application ID:** 10894933
- **Project number:** 5R01DK127277-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Erhu Cao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $635,357
- **Award type:** 5
- **Project period:** 2021-09-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894933

## Citation

> US National Institutes of Health, RePORTER application 10894933, A comprehensive map of polycystin channel regulation and its implications in polycystic kidney disease (5R01DK127277-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894933. Licensed CC0.

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