# Genetic code expansion and the study of CACNG proteins

> **NIH NIH R03** · UNIVERSITY OF ROCHESTER · 2021 · $154,000

## Abstract

PROJECT SUMMARY - ABSTRACT
AMPA receptors are critical components of excitatory synaptic transmission. The current view is that AMPA
receptors are nearly always accompanied by one or more types of auxiliary proteins. There are several families
of these including the CMPK, GSGL, CNIH and CACNG of which the CACNG is the best studied. The CACNG
proteins not only enhance the surface trafficking of AMPA receptors but also act as gain of function proteins,
increasing agonist efficacy and potency, open probability, and reducing desensitization. The various CACNG
proteins exert these effects to differing extents and thus detailed structure-function analysis of AMPA-auxiliary
complexes deepen our understanding of which portions of the channel control these biophysical properties.
Moreover, the diversity of CACNG proteins is a molecular handle by which distinct drugs, selective for specific
CACNG proteins, can be developed. To further these goals, we will leverage the power of genetic code
expansion, which enables non-canonical or unnatural amino acids with advantageous properties to be introduced
in specific locations. Within the funding period, we will compile cDNA libraries for 4 CACNG family members
which can be used to screen for non-canonical amino acid incorporation. We will also test these positons for
leakage and for Bpa incorporation using an innovative fluorescence and FRET based-approach. Finally, we will
confirm function using electrophysiology. Together, these resources and data will catalyze the investigation of
these IDG-program proteins using genetic code expansion. Further, our efforts may encourage the use of
powerful genetic code expansion techniques to study of IDG-proteins by other labs.

## Key facts

- **NIH application ID:** 10214790
- **Project number:** 1R03TR003619-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** David Malcolm MacLean
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $154,000
- **Award type:** 1
- **Project period:** 2021-04-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214790

## Citation

> US National Institutes of Health, RePORTER application 10214790, Genetic code expansion and the study of CACNG proteins (1R03TR003619-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10214790. Licensed CC0.

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