# Molecular mechanisms of photoreceptor disc morphogenesis

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $648,451

## Abstract

This proposal addresses one of the most fundamental unsolved problems in vision: the molecular and cellular
mechanism responsible for building and maintaining the light-sensitive organelle of vertebrate photoreceptor cells,
the outer segment. The outer segment is a ciliary structure filled with a stack of disc membranes, which provide
vast surfaces for light capture and harbor proteins comprising the phototransduction machinery. Discs are renewed
on a daily basis in order to counteract the adverse effects of light exposure, and the fidelity of disc renewal is critical
for maintaining photoreceptor health and normal vision. It is now well-established that the formation of each new
disc begins with an evagination of the ciliary plasma membrane driven by an expansion of branched actin network
in a mechanism akin the formation of lamellipodia in motile cells. What remain entirely unknown are the molecular
mechanism that initiate the formation of each new disc with the striking periodicity of approximately 80 times per
day in mammals. Pinpointing this mechanism is the overall goal of this application. Our recent work shows that this
actin network is nucleated by the WAVE protein complex whose unique subunit composition is specifically fitted to
perform this function. Because WAVE complexes mediate between the upstream signaling pathways and
downstream actin networks, this opens doors to elucidating the entire mechanism responsible for the periodic
assembly and disassembly of actin at the disc morphogenesis site. To accomplish this goal, we will combine the
efforts of two laboratories, which will contribute unique expertise and two complementary models of genetically
modified animals: mice and Xenopus frogs. Our proposed experiments will investigate the regulation of the actin
cytoskeleton dynamics, including that in living photoreceptors, by two classes of regulatory molecules: small
GTPases and phosphoinositides. Elucidating these mechanisms is critical for advancing our understanding of basic
photoreceptor cell biology and pathobiological mechanisms underlying photoreceptor degeneration frequently
associated with defects in outer segment morphogenesis.

## Key facts

- **NIH application ID:** 10929476
- **Project number:** 5R01EY035525-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Vadim Y Arshavsky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $648,451
- **Award type:** 5
- **Project period:** 2023-09-30 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929476

## Citation

> US National Institutes of Health, RePORTER application 10929476, Molecular mechanisms of photoreceptor disc morphogenesis (5R01EY035525-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10929476. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*