# Chibby and Its Associated Proteins in Ciliated Cell Differentiation

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2020 · $395,445

## Abstract

PD/PI: Takemaru, Ken-Ichi
Title: Chibby and Its Associated Proteins in Ciliated Cell Differentiation
PROJECT SUMMARY
 Motile multicilia are abundant in the respiratory tract and beat synchronously in waves to propel inhaled
debris and pathogens entrapped in mucus to the pharynx. This provides an important innate defense
mechanism against respiratory infections. Multicilia are usually found as clusters of 100 to 300 on the apical
surface of a ciliated cell in the respiratory epithelium. Dysfunction of multicilia has been linked to various
pulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), and primary ciliary
dyskinesia (PCD). Despite their clinical importance, little is known about the key molecules and mechanisms
that govern multiciliogenesis and ciliated cell differentiation. Therefore, understanding these fundamental
biological phenomena is crucial for developing novel therapeutic strategies for the prevention and treatment of
cilia-related pulmonary disorders. We previously demonstrated that the small coiled-coil protein Chibby (Cby)
localizes to the basal body (BB) of cilia and plays an essential role in ciliogenesis and differentiation of airway
ciliated cells in mice. More recently, we reported that during early stages of ciliated cell differentiation, Cby
facilitates efficient docking of BBs to the apical cell membrane via formation of membranous structures, called
ciliary vesicles (CVs). Mechanistically, Cby is recruited to BBs through protein-protein interactions with the
ciliopathy-associated protein CEP164. Cby then interacts with the membrane trafficking machinery component
Rabin8, a guanine nucleotide exchange factor (GEF) for the small GTPase Rab8, to promote the recruitment of
Rab8 and CV assembly. Cby may also play a role in biogenesis and homeostasis of the ciliary membrane
(CM) as it continues to localize at the base of elongating and mature cilia. However, the molecular components
and mechanisms of assembly of CVs and CMs and BB docking remain poorly understood. For this R01
proposal, we have established a conditional CEP164-KO mouse model to study its function during ciliated cell
differentiation in vivo. Furthermore, we have successfully identified bona fide Cby-interacting proteins, named
FAM92A and FAM92B, which harbor a membrane-binding Bin/Amphiphysin/Rvs (BAR) domain. We propose
to investigate their molecular roles in differentiation of airway ciliated cells. The overall goal of this proposal is
to elucidate the roles of Cby, CEP164, and FAM92 proteins in CV formation, BB docking, and ciliated cell
differentiation with the following Specific Aims: Specific Aim 1. Investigate the role of CEP164 in ciliated
cell differentiation; Specific Aim 2. Study the roles of FAM92A and FAM92B in ciliogenesis and ciliated
cell differentiation; Specific Aim 3. Elucidate the membrane-remodeling and vesicular properties of
FAM92A, 92B, and Cby. We anticipate that these experiments will contribute to a fundame...

## Key facts

- **NIH application ID:** 9999646
- **Project number:** 5R01HL139643-03
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** KEN-ICHI TAKEMARU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $395,445
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999646

## Citation

> US National Institutes of Health, RePORTER application 9999646, Chibby and Its Associated Proteins in Ciliated Cell Differentiation (5R01HL139643-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999646. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*