# Quality control of the primary cilium proteome

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $50,717

## Abstract

Primary cilia organize signaling pathways such as vision, olfaction and Hedgehog signaling. The 
movements of signaling receptors into, inside and out of cilium are critical for the correct 
regulation of these pathways, yet our understanding of the basic mechanisms governing signaling 
receptor trafficking through cilia remains fragmentary. Past work from the lab identified and 
characterized the BBSome, a protein complex that ferries signaling receptors out of cilia. The 
relevance of the BBSome to human health and disease is evidence by the fact that BBSome dysfunction 
causes Bardet-Biedl Syndrome (BBS), a hereditary disease characterized by obesity, retinal 
degeneration, polydactyly and kidney malformations.
The major goal of this proposal is to determine how the BBSome selects signaling receptors for 
removal from cilia. The emphasis in this funding period will be on investigating the role of 
ubiquitin in tagging membrane proteins for removal from cilia. Preliminary data indicate the 
existence of a ciliary machinery that recognizes activated GPCRs, ubiquitinates them and sorts 
ubiquitinated GPCRs out of cilia. We will characterize the molecules acting at each of these steps 
using quantitative assays for signal-dependent GPCR exit. The hierarchical ordering of the 
molecular cogs and levers that affix and read ubiquitin on proteins that need to exit cilia 
promises to uncover a multi-step pathway reminiscent of the ESCRT machinery responsible for 
degradative sorting. Finally, the fate of GPCRs that exit cilia will be tracked by single-molecule 
imaging to determine whether endocytosis is coupled to ciliary exit or whether GPCRs instead 
diffuse into the plasma membrane after exiting cilia.
The proposed studies will cast new light on how the ciliary abundance of proteins is regulated and 
open the door to a mechanistic investigation of ciliary quality control.

## Key facts

- **NIH application ID:** 10135627
- **Project number:** 3R01GM089933-11S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Maxence V Nachury
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,717
- **Award type:** 3
- **Project period:** 2010-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135627

## Citation

> US National Institutes of Health, RePORTER application 10135627, Quality control of the primary cilium proteome (3R01GM089933-11S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10135627. Licensed CC0.

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