# Rhodopsin Trafficking & Photoreceptor Membrane Renewal

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2022 · $367,387

## Abstract

Project Summary
The long-term goal of the proposed research is to improve the understanding of the
molecular mechanisms by which mutations in genes that regulate rhodopsin trafficking
and photoreceptor membrane renewal lead to retinal diseases. Mutations in rhodopsin
that affect its targeting motif cause severe forms of autosomal dominant retinitis
pigmentosa (ADRP). In the course of our research, we defined the rhodopsin C-terminal
VxPx motif as a conserved ciliary targeting signal. Furthermore, we identified a ciliary
targeting complex that recognizes this signal and regulates sorting into post-Golgi
rhodopsin transport carriers (RTCs). Our previous studies revealed that membrane
targeting to the rod outer segments (ROS) is a conserved form of ciliary targeting, and
that the complex we identified is a conserved complex that targets sensory receptors to
primary cilia through intricate functional networks of small GTPases and their regulators
that are exquisitely sensitive to mutations causing retinal degenerations and ciliopathies.
We now propose to define the function of the Rab8 GEF Rabin8, and determine whether
and how its phosphorylation by NDR2/STK38L kinase, a product of (erd) retinal
degeneration gene, controls rhodopsin trafficking and ciliogenesis. We will also delineate
the molecular mechanisms regulating Rabin8 interactions with the R-SNARE VAMP7,
and determine how their dysfunction affects ROS membrane trafficking. To accomplish
this, we will use our established cell-free system that reconstitutes rhodopsin trafficking
in vitro and probe molecular interactions by kinase assays, and pulldown experiments
with recombinant and purified components—as well as by transgenic expression of
mutant and phosphomimetic protein constructs, confocal microscopy, Correlative Light
and Electron Microscopy (CLEM), Super Resolution (SR) direct Stochastic Optical
Reconstruction Microscopy (dSTORM) imaging, and immunoprecipitation from
transgenic retinas with anti-GFP antibody followed by LC-MS/MS analysis. The basic
understanding of the molecular linkage between the regulatory machineries involved in
the renewal of light-sensitive membranes through ciliary targeting and a wide range of
systemic cilia disorders is expected to provide the foundation for improved therapeutic
strategies to treat retina-specific and syndromic forms of photoreceptor loss.

## Key facts

- **NIH application ID:** 10356045
- **Project number:** 5R01EY012421-20
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** DUSANKA Danielle DERETIC
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $367,387
- **Award type:** 5
- **Project period:** 1999-01-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356045

## Citation

> US National Institutes of Health, RePORTER application 10356045, Rhodopsin Trafficking & Photoreceptor Membrane Renewal (5R01EY012421-20). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10356045. Licensed CC0.

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