# Protein Targeting in Vertebrate Photoreceptors

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $381,250

## Abstract

PROJECT SUMMARY:
Vertebrate photoreceptors are an elegant example of form being finely tuned to support function. These
primary sensory neurons are linearly organized into a series of morphologically and functionally distinct
compartments. All of the compartments contribute in different ways to the maintenance and signaling activity of
this neuron. For instance, photons are captured in the outer segment, the synapse communicates that event to
downstream neurons, and the inner segment, typically thought of as the housekeeping compartment, houses
the ion channels, pumps, and transporters needed to set and maintain the circulating current that is ultimately
used to communicate the presence or absence of light. The polarized trafficking of select ion channels to the
different photoreceptor compartments is well recognized as essential for the health and function of this cell.
Yet, the mechanisms controlling the subcellular trafficking and localization of ion channels in this cell or for that
matter, most others, is poorly understood at best. The overarching goal of this project is to identify the
mechanisms that control polarized protein trafficking in photoreceptors. In this proposal we are building on the
knowledge we gained in our earlier studies of HCN1, a hyperpolarization activated channel that filters light
responses and is essential for vision in bright light. Aim 1 probes how the assembly status and permissiveness
of HCN1 to leave the ER is coordinated. This aim also tests if the mechanisms controlling HCN1 processing
are used to regulate Kv2.1/Kv8.2, a related ion channel also found within the inner segment that when absent
results in aberrant signaling and cone dystrophy. Aim 2 probes the function and mechanism of a second
trafficking signal within HCN1 that we propose is required, at least in part, to recruit the protein coat needed for
the generation of HCN1-bearing transport vesicles. A suite of genetic, biochemical, imaging, and physiological
tools are used. Altogether, this work will reveal fundamental mechanisms used in the polarized trafficking of
photoreceptor proteins, shed light on the contributions made by the early secretory pathway to the regulation of
ion channels, and is anticipated to transform current views of the fundamental organization of photoreceptors
in health and disease.

## Key facts

- **NIH application ID:** 9856455
- **Project number:** 5R01EY020542-10
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Sheila A Baker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2010-04-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856455

## Citation

> US National Institutes of Health, RePORTER application 9856455, Protein Targeting in Vertebrate Photoreceptors (5R01EY020542-10). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9856455. Licensed CC0.

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