# Understanding the functions of USH2A and ADGRV1 in photoreceptors by identifying their interacting proteins

> **NIH NIH R21** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $228,750

## Abstract

Project Summary
Usherin (USH2A) and adhesion G protein-coupled receptor V1 (ADGRV1) are two large transmembrane
proteins in the periciliary membrane complex (PMC) in photoreceptors. Mutations in the genes encoding these
two proteins disrupt the PMC and lead to autosomal recessive retinitis pigmentosa (arRP) and Usher
syndrome (USH). The USH2A gene is the most common causative gene for arRP and USH. The latter is a
condition of arRP combined with hearing loss and is the leading cause of inherited deaf-blindness in the world.
Both arRP and USH patients experience early night and peripheral vision loss and become completely or
legally blind eventually. Currently, no cure is available for arRP or USH. At the PMC in photoreceptors, USH2A
and ADGRV1 interact with a scaffold protein whirlin (WHRN) through their PDZ-binding motif at the intracellular
C-terminus. Among the three proteins, our previous studies suggest that ADGRV1 plays the most important
role in the PMC. However, the functions of USH2A and ADGRV1 remain largely unknown, because the
majority region of these two proteins is located outside photoreceptors and has not been well studied. Our
preliminary studies using immunoprecipitation and tagged protein pull-down assays coupled with mass
spectrometry identified several USH2A- and ADGRV1-interacting candidate proteins in bovine and mouse
retinas. Some of these interactions were confirmed by coimmunoprecipitation and colocalization in mouse
retinas or by pull-down assays using recombinant proteins. Based on these initial findings, we propose to
conduct a comprehensive, non-biased analysis of USH2A and ADGRV1 ectodomain-interacting proteins. In
Aim 1, potential extracellular USH2A- and ADGRV1-interacting proteins will be identified from bovine retinal
lysates by pull-down assays using ectodomain baits, coupled with mass spectrometry. In Aim 2, the identified
potential USH2A and ADGRV1 ectodomain-interacting proteins will be confirmed in mice and monkeys by
standard biochemical binding assays and localization studies, and the effect of known USH2A and ADGRV1
pathogenic missense mutations on these interactions will be examined. The findings of this study will provide
novel insights into PMC function in photoreceptors and the pathogenesis of retinal degeneration caused by
USH2A and ADGRV1 defects.

## Key facts

- **NIH application ID:** 9891346
- **Project number:** 1R21EY030198-01A1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Jun Yang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,750
- **Award type:** 1
- **Project period:** 2020-02-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891346

## Citation

> US National Institutes of Health, RePORTER application 9891346, Understanding the functions of USH2A and ADGRV1 in photoreceptors by identifying their interacting proteins (1R21EY030198-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9891346. Licensed CC0.

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