# UV to blue neuronal phototransduction mechanisms

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $422,835

## Abstract

Cryptochrome (CRY) transduces ultraviolet and blue wavelength light to rapid changes in neuronal membrane
potential of lateral ventral circadian/arousal neurons in Drosophila brains by a redox based mechanism via
voltage-gated K+ channel beta subunits that express a functional redox sensor that couples light activated
CRY to depolarization of the neuronal membrane. Recently, we found that Rhodopsin 7 (Rh7) is an extra-
retinal opsin that also expresses in the lateral ventral neurons and transduces violet light to depolarization and
increased neuronal firing rate. Light activated Rh7 couples to multiple G-protein pathways. Thus, we have
contributed to the discovery of two novel phototransduction that occur in central brain neurons. CRY and Rh7
interact in the lateral ventral neurons, which receive a third photic input synaptically from external
photoreceptors. This raises a new set of questions of signaling interactions between redox-based CRY and a
G protein-coupled opsin in the same neurons along with further modulation from light driven synaptic inputs.
Using an integrative approach based on powerful molecular genetics and behavioral analysis and physiology,
we find that CRY expressed in fly neurons regulates UV phototaxis and other light driven behaviors including
executive choice. Our most recent work shows that these signaling mechanisms that drive complex light
response behaviors are highly sensitive to circadian time of day effects, even diurnal vs. nocturnal preferences.
The interactions between CRY and Rh7 provide precise time-of-day information to flies, which we can monitor
by circadian whole circuit imaging at single cell resolution. The opportunities are enormous because
heretofore, our understanding of short wavelength light sensing in invertebrates, including harmful insects such
as mosquitoes has been limited to retinal opsin-based phototransduction. We propose to determine how these
short wavelength phototransduction systems converge to a small number of neurons to drive light responses
and time of day behavior in flies and mosquitoes. Our research provides new opportunities to improve light
control of insects by understanding the fundamental biology of novel redox and G-protein based light signaling
mechanisms.

## Key facts

- **NIH application ID:** 10140378
- **Project number:** 5R35GM127102-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Todd C Holmes
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $422,835
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140378

## Citation

> US National Institutes of Health, RePORTER application 10140378, UV to blue neuronal phototransduction mechanisms (5R35GM127102-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10140378. Licensed CC0.

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