# Nephronophthisis-related ciliopathies and ciliary compartmentalization

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2020 · $347,043

## Abstract

Project Summary
Cilia are cellular organelles that are essential for human development and health. It has long been known that
cilia are organized into structurally and functionally distinct compartments known as the basal body, the
transition zone, and the cilia shaft. Nephronophthisis-related ciliopathy (NPHP-RC) proteins localize to
subregions within the previously known compartments, revealing a hidden complexity. For example,
NPHP2/Inversin localizes to a proximal region of the ciliary shaft called the Inversin Compartment (InvC) that is
not identifiable by any ultrastructural features. Despite the profound medical importance of cilia in human
health and disease, how the ciliary shaft is spatially and functionally organized remains poorly understood.
Identifying mechanisms controlling cilia shaft compartmentalization and understanding the physiological
relevance of ciliary territories will be important in identifying therapeutic targets to combat cystic kidney
diseases and other ciliopathies. The InvC is conserved in the nematode C. elegans, suggesting that the logic
underlying the establishment of the InvC and ciliary compartmentalization is similar in worm and human cilia. In
C. elegans, we found that the InvC regulates microtubule patterning and tubulin glutamylation. We also
discovered that the Tubulin Code – via tubulin isotypes and tubulin post-translational modifications – sculpts
ciliary structure, ciliary motor-based transport, and ciliary functions including release of ciliary extracellular
vesicles. In this new application, we use C. elegans, an exceptional model for ciliary biology and human
ciliopathies, to address the question of how the cilium is spatially and functional organized. First, we will define
the origin and function of the InvC and examine the relationship between the InvC and tubulin glutamylation.
Second, we determine how the Tubulin Code regulates microtubule ultrastructure, motor-based intraflagellar
transport, and specialized ciliary functions. Finally, we will identify new genes and pathways that control ciliary
homeostasis and protect against ciliary degeneration. This research will address the medically relevant
question of how cilia are structurally and functionally organized in healthy and diseased states, and will provide
fundamental insight to the molecules, mechanisms, and functions of ciliary compartmentalization and the
Tubulin Code. These studies have direct implications for cystic kidney disease research because many of the
genes and pathways explored in our work are associated with ciliopathies.

## Key facts

- **NIH application ID:** 9849265
- **Project number:** 5R01DK116606-03
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Maureen M Barr
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $347,043
- **Award type:** 5
- **Project period:** 2017-12-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849265

## Citation

> US National Institutes of Health, RePORTER application 9849265, Nephronophthisis-related ciliopathies and ciliary compartmentalization (5R01DK116606-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9849265. Licensed CC0.

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