# Novel function of beta-catenin in regulation of RPE basal membrane

> **NIH NIH R21** · UNIVERSITY OF LOUISVILLE · 2021 · $189,150

## Abstract

PROJECT SUMMARY/ABSTRACT
The RPE acts as a blood outer retinal barrier transporting nutrients from the choroid circulation to adjacent
photoreceptors. Apical microvilli on the RPE are critical for interdigitating interaction with photoreceptor outer
segments. The basal membrane of the RPE differentiates into a heavily folded plasma membrane system to
form a specialized organelle, called basal infolding. These infoldings dramatically increases the surface area to
enhance diffusion and transporter-assisted flux of solutes, factors, nutrients, and metabolites. How the infolding
arises and its potential relevance to RPE biology has not been explored. In preliminary results, we demonstrate
that this infolding is mediated by -catenin in a complex with N- and P-cadherins/-catenin, and cytoplasmic -
catenin is required for the integrity of basal membrane infolding. We hypothesize that the increase in surface
area resulting from membrane infolding is critical for efficient nutrient transport. Similar membrane infolding
increases surface area at the blood brain barrier, the intestinal lumen and kidney tubules that serve as a blood-
urine barrier. Consistent with functional inhibition of nutrient transport, mouse -catenin mutants show
shortening of adjacent photoreceptor outer segments, which depend upon nutrients transported through the
RPE. In this proposal, we will test whether the -catenin/cadherin complex stabilizes the RPE basal infoldings
for maintaining the basal infolding integrity and ensuring efficient transport of nutrients and metabolites across
the RPE barrier. Inadequate metabolic support from RPE has been linked to several aspects of age-related
macular degeneration, as have mutations in P-cadherin and α-catenin. As such, the β-catenin conditional
knockout mouse represents an important model to study the etiology and pathogenesis of RPE dystrophy and
retinal degeneration. Our study will provide a novel mechanism for the integrity of RPE basal infoldings and its
relevance to RPE function, which may give insight into the pathogenesis of RPE dystrophy and AMD, even
some of renal diseases.

## Key facts

- **NIH application ID:** 10242747
- **Project number:** 5R21EY030225-02
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Qingxian Lu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $189,150
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242747

## Citation

> US National Institutes of Health, RePORTER application 10242747, Novel function of beta-catenin in regulation of RPE basal membrane (5R21EY030225-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10242747. Licensed CC0.

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