# Molecular Organization of the First Visual Synapse

> **NIH NIH R01** · SCRIPPS FLORIDA · 2022 · $1

## Abstract

PROJECT SUMMARY
 Mammalian rod and cone photoreceptors are indispensible for vision. They convert light into electrical
response, which is then propagated to the downstream neurons, the ON-bipolar cells (ON-BC). Deficits in
synaptic communication with the ON-bipolar neurons are known to cause congenital stationary blindness in
humans, a condition characterized by poor light sensitivity and frequent co-morbidity with many other ocular
conditions. Our long-term goal is to elucidate molecular and cellular mechanisms of signal transmission at
photoreceptor to ON-bipolar synapse with the hope to better understand blinding conditions and devising
strategies for their treatment.
 During the last several years we and others have identified a number of molecules that enable synaptic
transmission of photoreceptor signals. In addition to canonical pre- and post- synaptic elements that coordinate
neurotransmitter release and its reception, these include several cell adhesion-like molecules with poorly
understood functions. Intriguingly, our work over the previous funding period suggested that these emerging
molecules are engaged in trans-synaptic bridging of presynaptic release machinery of photoreceptors with
postsynaptic receptors in the ON-BC. Specifically, we found that the key postsynaptic receptor mGluR6 on ON-
BC interacts with a cell-adhesion molecule: ELFN1 in rods and ELFN2 in cones. Similarly, the orphan receptor
GPR179 that negatively regulates mGluR6 signaling in the ON-BC interacts with pre-synaptic dystroglycan
complex (DGC) in photoreceptors.
 These observations lead to the central hypothesis of the proposal that precise synaptic
communication of photoreceptors with the downstream ON-BC requires assembly of the signaling complex
where interactions between individual elements are tightly orchestrated. We plan on testing this hypothesis by
pursuing two complementary Specific Aims that will: 1) determine the roles and mechanisms of ELFN
proteins in photoreceptors and 2) delineate the organization and function of trans-synaptic DGC-orphan
receptor GPR179 complex. The strategy proposed to address these Aims will entail a synergistic combination
of biochemical, cell biological, and physiological approaches exploiting a powerful array of precise tools and
animal models.
 Better understanding of synaptic mechanisms of photoreceptors will yield important insights into light
sensory function of the retina and may suggest novel nodes of intervention for treating inherited types of night
blindness.

## Key facts

- **NIH application ID:** 10329993
- **Project number:** 5R01EY018139-15
- **Recipient organization:** SCRIPPS FLORIDA
- **Principal Investigator:** Kirill A. Martemyanov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1
- **Award type:** 5
- **Project period:** 2007-04-01 → 2022-04-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10329993

## Citation

> US National Institutes of Health, RePORTER application 10329993, Molecular Organization of the First Visual Synapse (5R01EY018139-15). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10329993. Licensed CC0.

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