# Membrane targeting calcium sensors in vision

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $380,725

## Abstract

The overall objectives are to develop nuclear magnetic resonance (NMR) techniques and use
them in concert with experimental functional approaches to elucidate the molecular structure and
physiologic functions of selected membrane-targeting proteins involved in phototransduction in
vision and other signal transduction processes. During the next five years, we will use nuclear
magnetic resonance (NMR), fluorescence, microcalorimetry, spin-label EPR, xray crystallography,
and computational analysis to delineate the structure, dynamics and mechanisms of a family of
neuronal calcium sensor proteins (calcium-myristoyl switches) that serve as membrane-
targeting regulators in calcium signaling and are linked to retinal and neurological diseases. Our
studies will determine the structural basis of: (1) retinal guanylyl cyclase (RetGC) regulation by
GCAP1 and retinal degeneration 3 (RD3) protein, and their role in autosomal dominant cone
dystrophy and Leber Congenital Amaurosis; (2) Ca2+-dependent inactivation of photoreceptor
cyclic nucleotide gated (CNG) channels controlled by calmodulin (CaM); and (3) Ca2+-dependent
activation of retinal L-type Ca2+ channels (CaV1.4) mediated by calcium binding protein-4
(CaBP4), and implicated in congenital stationary night blindness. By continuing our intensive
structural analysis of retinal Ca2+ sensor proteins and by broadening the scope to encompass
membrane trafficking regulators (RD3) and protein targets (RetGCs and ion channels), we hope to
gain an atomic-level understanding of how retinal calcium sensor proteins regulate their
membrane-bound target proteins in retinal disease processes. The specific aims are 3-fold: (1)
Determine atomic-level structures of GCAP1 and RD3 each bound to RetGC to elucidate activation
mechanism of RetGCs and thus provide a structural basis for understanding mechanisms of visual
recovery and retinal degenerative diseases; (2) Determine structures of CaM bound to CNG
channels to understand molecular mechanisms of light-adaptation in rod and cone photoreceptors;
(3) Determine atomic-level structures of the retinal calcium sensor protein (CaBP4) bound to the
retinal L-type voltage-gated Ca2+ channel (CaV1.4) at the rod synapse to understand the Ca2+-
dependent regulatory mechanism of ion channels linked to congenital stationary night blindness.

## Key facts

- **NIH application ID:** 10455705
- **Project number:** 5R01EY012347-25
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** JAMES B AMES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $380,725
- **Award type:** 5
- **Project period:** 1999-01-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455705

## Citation

> US National Institutes of Health, RePORTER application 10455705, Membrane targeting calcium sensors in vision (5R01EY012347-25). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10455705. Licensed CC0.

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