# The Role of EPB41L5 in Regulation of Cilia Function

> **NIH NIH R03** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $84,750

## Abstract

Summary
Developmental defects are substantial contributors to morbidity and mortality in the US as well as worldwide.
While considerable progress has been made to begin to understand the underlying biology that contributes to
these defects, much remains poorly understood. We study morphogenesis in which cells rearrange
cytoskeletal organization in response to signals from its surrounding environments. Defects in this process
during embryogenesis cause birth defects and developmental problems. Our long-term goal is a more
comprehensive understanding of morphogenesis: how a cell responds to signals from its environment and
remodels the cytoskeleton in developing embryos where dynamic rearrangement of the cytoskeleton is the
major driving force of morphogenesis. This is essential to advance our understanding of congenital and
postnatal disorders in which cytoskeletal rearrangement is the underlying source of the defect. This proposed
research is aimed at exploring a novel role of Erythrocyte membrane protein band 4.1 like 5 (Epb41l5) in the
regulation of ciliary function. Cilia are hair like extensions from the apical surface to receive signals. Epb41l5 is
a scaffold protein that mediates association of cytosolic proteins with proteins at the plasma membrane.
Epb41l5 regulates a number of cellular processes that require remodeling of the actin cytoskeleton, in
particular actin at the apical cortex. While previous studies reported cilia dysfunction in epb41l5 null mouse
embryos, these studies concluded that the defects in cilia were secondary to defects of other Epb41l5
functions such as apical-basal polarity formation. Our preliminary data, however, suggests that Epb41l5 could
have a direct role in regulating ciliary function. We established novel alleles of zebrafish epb41l5 mutants
which showed normal apicobasal polarity formation but showed phenotypes associated with cilia dysfunction.
We identified Nephrocystin 5 (NHPH5) as a novel Epb41l5 interacting protein. NPHP5 mutations were
originally identified in patients with Nephronophthisis and NPHP5 has shown to regulate cilia function. Our
hypothesis is that: Epb41l5 regulates ciliary function by inhibiting NPHP5 localization at cilia. We will test the
hypothesis using mammalian cell culture system and zebrafish embryos, an established vertebrate genetic
model that is accessible for experimental manipulation and imaging at all developmental stages. Completion of
this study will lead to further understanding of regulatory mechanisms of ciliary function, which is necessary for
developing more effective therapeutic strategies to combat ciliopathies. We believe that this study is highly cost
effective and will produce data that lays the basis for a future R01.

## Key facts

- **NIH application ID:** 10053505
- **Project number:** 7R03HD094980-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Miho Matsuda
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $84,750
- **Award type:** 7
- **Project period:** 2019-11-07 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053505

## Citation

> US National Institutes of Health, RePORTER application 10053505, The Role of EPB41L5 in Regulation of Cilia Function (7R03HD094980-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10053505. Licensed CC0.

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