# Phototransduction and Signaling in Photoreceptors

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $409,375

## Abstract

PROJECT SUMMARY
 There have been great advances over the past 30-40 years in understanding how light initiates vision in
the rod and cone photoreceptors of the eye. Not only is the sequence of events in this process known, but the
genes coding for the key phototransduction proteins have also been cloned. Mutations of many of these genes
are found to be associated with various vision-impairing diseases.
 Phototransduction starts with the visual pigment. Several years ago, we made major advances by
showing that the dark spontaneous activity of rod and cone pigments indeed comes from canonical
isomerization of these pigments albeit being driven by thermal instead of light energy. We developed a theory
able to predict quantitatively the 107-fold range in thermal activity across rod and cone pigments in the visible
spectrum. Our theory as originally developed describes very successfully the behavior of canonical rod and
cone pigments, but we have now found it to be equally applicable to a non-canonical, hybrid pigment with both
rod-pigment-like and cone-pigment-like properties. In Aim 1, we propose to check the theory against several
unusual native pigments and also a disease-causing mutant pigment for testing the theory's overall predictive
power. Separately, the first step of signal amplification in rod phototransduction consists of a large number of
downstream G protein molecules being activated by each photoexcited rhodopsin, with the amplification factor
traditionally believed to be ~1,000, but now under debate. In Aim 2, we shall evaluate directly the true
amplification value in situ. Upon light off, phototransduction needs to terminate. The inactivation of
photoexcited rhodopsin is initiated by its phosphorylation followed quickly by the binding of the capping protein,
arrestin, which translocates massively to the rod outer segment from the inner segment, cell body and synaptic
terminal in bright light. In Aim 3, we shall examine the signaling underlying this arrestin translocation. Finally,
for short Aim 4, we shall examine a potential mechanism whereby the βγ-subunits of rod transducin may
contribute to the deactivation of the cGMP-phosphodiesterase, the enzyme that is activated by transducin-α
and hydrolyzes cGMP to produce the hyperpolarizing light response.
 Sorting out the above questions will help understand not only normal photoreceptor physiology, but also
the pathophysiology underlying disease conditions.

## Key facts

- **NIH application ID:** 9910391
- **Project number:** 5R01EY006837-33
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** KING-WAI YAU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,375
- **Award type:** 5
- **Project period:** 1987-02-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910391

## Citation

> US National Institutes of Health, RePORTER application 9910391, Phototransduction and Signaling in Photoreceptors (5R01EY006837-33). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9910391. Licensed CC0.

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