# Structural landscape of photoreceptor synapses

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2022 · $483,000

## Abstract

PROJECT SUMMARY
 Rod and cone photoreceptors are indispensable for our vision. Their death or dysfunction is an underlying
cause for a vast majority of blinding retina conditions. Key to photoreceptor function is the ability to transmit the
signal that they generate in response to light to other neurons in the retina for processing of visual signals and
their communication to the brain. For this to occur, photoreceptors form elaborate synapses with the
downstream neurons, the bipolar cells (BC). Deficits in synaptic communication between photoreceptors and
bipolar cells are known to cause congenital stationary blindness in humans, various forms of rod/cone
dystrophies and frequent co-morbidity with many other ocular conditions. The long term goal of our collaborative
program is to obtain atomic level view of molecular organization of machinery that enable synaptic
communication of the photoreceptors with the hope to better understand blinding conditions and devising
strategies for their treatment.
 Recent research from our laboratories and others have identified several molecules critical for the
synaptic communication of photoreceptors. We have further discovered that many of these components are
scaffolded into macromolecular assemblies that span the synaptic cleft and physically integrate pre-synaptic
elements of photoreceptors with post-synaptic receptors in BC. Specifically, we found that the postsynaptic
receptor on BC: mGluR6 interacts with two cell-adhesion molecules in photoreceptors: ELFN1 and ELFN2.
Furthermore, the machinery that drives excitation of BC in response to synaptic photoreceptor inputs is
associated with an orphan receptor GPR179 which in turn is integrated with pre-synaptic cell adhesion-like
molecule pikachurin (Pika) in photoreceptors. We also documented that loss of this organization abolishes
synaptic transmission leading to night blindness. However, at the moment we know absolutely nothing about
structural basis of these trans-synaptic complexes.
 Proposed studies aim to fill this gap by determining the atomic structures of the key trans-synaptic
scaffolds: ELFN1-mGluR6 and Pika-GPR179 complexes and probing their biochemical mechanisms. This will
be achieved by highly synergistic international collaboration leveraging expertise in biochemistry and cell biology
of photoreceptor synaptic proteins and recent advances in high resolution cryogenic electron microscopy
(CryoEM) to obtain high resolution molecular structures of the complexes probing their mechanisms at
exceedingly precise level. The premise of this proposal is that understanding synaptic organization of
photoreceptors would lead to novel therapeutic strategies for ameliorating blindness.

## Key facts

- **NIH application ID:** 10522890
- **Project number:** 1R01EY034339-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Kirill A. Martemyanov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $483,000
- **Award type:** 1
- **Project period:** 2022-09-30 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522890

## Citation

> US National Institutes of Health, RePORTER application 10522890, Structural landscape of photoreceptor synapses (1R01EY034339-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10522890. Licensed CC0.

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