# Function of CEP290 protein in retinal ciliopathies and normal photoreceptor structure and function.

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2020 · $43,894

## Abstract

Project Summary. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by
retinal degeneration (RD), obesity, polydactyly, renal defects, and genital defects. This proposal focuses on
one BBS-associated gene, Centrosomal protein of 290 kDa (CEP290), with the goal of understanding the role
of CEP290 in the normal structure and function of the rod sensory cilium, and the mechanisms of
pathophysiology in RD caused by CEP290 deficiency. CEP290 was chosen because depending on the allele
and background, CEP290 defects cause an array of diverse defects, all involving RD. In contrast to most other
BBS gene products, CEP290 protein does not form a stable part of the BBSome membrane coat complex, but
it interacts functionally and physically with other BBS proteins. While CEP290 has been proposed to be a
ciliary gate-keeper or a structural scaffold within the connecting cilium (CC), the field is currently divided on the
localization and the structural and functional roles of CEP290 within the CC, and the mechanism for CEP290
regulation of ciliary trafficking is not well understood. The Specific Aims are: 1. Chronology of CEP290
(BBS14) Subcellular Localization and BBS Protein Localization in CEP290- or BBS4-Mediated Retinal
Degeneration To test the hypothesis that CEP290 localizes peripherally to microtubule doublets and elucidate
the structural role of CEP290, the superresolution imaging techniques, Structured Illumination Microscopy
(SIM) and Stochastic Optical Reconstruction Microscopy (STORM) will be used. To assess the hypothesis that
mislocalization of interacting proteins such as BBS4 and BBS8,in CEP290-mediated RD is the direct result of
the absence of CEP290, the localization of BBS4 over the course of RD will be tracked as well as CEP290
localization in BBS4-mediated RD. To correlate mislocalization with disease progression over time, histology,
Optical Coherence Tomography (OCT), Transmission Electron Microscopy (TEM), and electroretinography
(ERG) will be used. 2. Identification of the BBSome Interacting Domains of CEP290. BBS4 and BBS8 are
BBSome subunits that both depend on the presence of CEP290 for proper localization. To test the hypotheses
that CEP290 interacts with BBS4 and BBS8 through its N-terminal SMC homology domain, and that BBS4 and
BBS8 interact with CEP290 through their tetratricopeptide repeats (TPR) domains, the proposed domains, or
full length proteins with and without mutations within the proposed interaction domains, will be expressed in
hRPE1 cells and tests for both proper co-localization and co-immunoprecipitation will be performed. 3.
Functional Rescue of Retinal Degeneration with In Vivo CEP290 domain Expression. To determine the in
vivo role of CEP290 and its domains in protein mislocalization, CEP290 mutant mice will receive sub-retinal
injections and electroporation of expression constructs for rescue domains and full-length CEP290 protein.
Understanding the functions and disease mechanism...

## Key facts

- **NIH application ID:** 9912768
- **Project number:** 5F31EY028025-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Valencia Potter
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $43,894
- **Award type:** 5
- **Project period:** 2017-05-08 → 2021-05-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912768

## Citation

> US National Institutes of Health, RePORTER application 9912768, Function of CEP290 protein in retinal ciliopathies and normal photoreceptor structure and function. (5F31EY028025-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9912768. Licensed CC0.

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