# Quality control of the primary cilium proteome

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $372,630

## Abstract

PROJECT SUMMARY
 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:** 9897420
- **Project number:** 2R01GM089933-11
- **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:** $372,630
- **Award type:** 2
- **Project period:** 2010-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897420

## Citation

> US National Institutes of Health, RePORTER application 9897420, Quality control of the primary cilium proteome (2R01GM089933-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897420. Licensed CC0.

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