# Proteomic and Transcriptional Analysis of Cilia-Dependent Dopamine Receptor 1 Signaling

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2020 · $195,000

## Abstract

ABSTRACT
Modulation of dopaminergic signaling has therapeutic potential for numerous neurological conditions, including
movement disorders, drug addiction, and anxiety disorders. One promising approach for modulation of
dopaminergic pathways involves targeting specific dopamine receptors to differentially regulate individual
signaling pathways. Yet, significant gaps in our understanding of dopamine receptor signaling remain and
hinder such efforts. We have discovered that dopamine receptor 1 (D1) dynamically localizes to primary cilia
on neurons in several brain regions, including the striatum. Primary cilia are cellular appendages that provide
critical sensory and signaling functions. Numerous human diseases are now known to be caused by defects in
primary cilia. Remarkably, we still know very little about how primary cilia impact neuronal function, despite the
fact that most, if not all, central neurons in the mammalian brain possess a primary cilium. Primary cilia are
restricted compartments and select G protein-coupled receptors (GPCRs), such as D1, are targeted to the
ciliary membrane in neurons. Downstream effectors of GPCR signaling also localize to neuronal cilia,
suggesting that primary cilia support specialized non-synaptic dopaminergic signaling. Indeed, we have
discovered that disrupting cilia in D1-expressing neurons results in deficient D1 signaling, as well as reduced
basal locomotor activity and obesity. In this proposal we will use cutting-edge approaches to identify the
molecular mechanisms underlying the role of cilia in D1-expressing neurons and provide critical insight into the
importance of cilia in D1 signaling. The outcomes of this work will fundamentally advance our understanding of
D1 signaling in the striatum and may implicate cilia-specific factors as novel targets for therapeutics.

## Key facts

- **NIH application ID:** 10017361
- **Project number:** 5R21MH121744-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** KIRK A MYKYTYN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,000
- **Award type:** 5
- **Project period:** 2019-09-12 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017361

## Citation

> US National Institutes of Health, RePORTER application 10017361, Proteomic and Transcriptional Analysis of Cilia-Dependent Dopamine Receptor 1 Signaling (5R21MH121744-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10017361. Licensed CC0.

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