# Administrative Supplement - Neuronal Gai-GPCR targeting to primary cilia and impact on cAMP mediated transcription

> **NIH NIH K01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $54,000

## Abstract

PROJECT SUMMARY / ABSTRACT
Ciliopathies are a collection of diseases that feature genetic mutations that impair primary cilia morphology or
function and are characterized by symptoms that include developmental disorders, obesity, cognitive and
behavioral deficits in humans. Primary cilia are immotile organelles that protrude off neuronal soma often
adjacent to the nuclear compartment. A growing body of evidence indicates that extracellular stimuli (i.e.,
neuromodulators) transmits specialized signaling through G protein-coupled receptors (GPCRs) located on
neuronal primary cilia to influence transcriptional changes and neuronal activity. Thus, determining how to
specifically target neuronal ciliary GPCRs, will lead to novel therapeutic approaches for neurological and
neuropsychiatric diseases. This proposal will focus on identifying selective ciliary targeting mechanics employed
by neural Gαi-coupled GPCRs and the impact of ciliary GPCR signaling on gene transcription.
We found that in brain sections, neural Gαi-coupled GPCRs, such as the mu opioid receptor, are expressed in
neuronal primary cilia of some neuronal populations but not others suggesting cell and/or receptor-selective
ciliary targeting machinery. In Specific Aim 1, we dissect whether ciliary targeting mechanics are cell-specific
and/or receptor-selective in three distinct cell types. In Specific Aim 2, we employ Proteomics-based approaches
to identify novel GPCR-associated proteins involved in ciliary targeting of Gαi-coupled GPCRs in cells and brain
tissue. In Specific Aim 3, we will evaluate the contribution of ciliary Gαi-coupled GPCR cyclic-AMP signaling to
neuronal transcription. Collectively, this proposal will attempt to discern the mechanisms underlying ciliary
targeting of neuronal GPCRs and the neuromodulatory function of ciliary GPCRs.

## Key facts

- **NIH application ID:** 10696892
- **Project number:** 3K01MH123757-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Aliza Toby Ehrlich
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $54,000
- **Award type:** 3
- **Project period:** 2020-07-01 → 2024-12-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10696892

## Citation

> US National Institutes of Health, RePORTER application 10696892, Administrative Supplement - Neuronal Gai-GPCR targeting to primary cilia and impact on cAMP mediated transcription (3K01MH123757-03S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10696892. Licensed CC0.

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