# Investigating the role of TBC1D19 in microtubule dynamics, ciliation and organelle morphology

> **NIH NIH F31** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $48,974

## Abstract

PROJECT SUMMARY
Primary cilia are evolutionarily conserved cellular antennas comprised of a microtubular (MT) axoneme
enveloped by a lipid sheath. They are found at the surface of most mammalian cells that have terminally
differentiated or entered quiescence. Interestingly, cilia are enriched for proteins required to transduce Sonic
Hedgehog and Wnt signaling. Indeed, defects in cilia have been linked to both developmental disorders and
cancer, reflecting its intimate relationship with particular signaling pathways that control cell cycle and
polarization. Ciliogenesis requires the coordination of multiple events: (1) timely recruitment of various Rab
GTPase-positive vesicles to the mother centriole; (2) basal body migration to the plasma membrane; and (3)
growth of microtubules to assemble the ciliary axoneme. MT dynamics are controlled by post translational
modifications (PTMs), such as glutamylation, and the ciliary axoneme is highly poly-glutamylated. Poly-
glutamylation is mediated by a family of tubulin tyrosine-like ligases (TTLLs), including TTLL1, which the
Dynlacht laboratory has extensively characterized. Unlike other TTLLs, TTLL1 forms a multimeric Tubulin Poly-
glutamylation Complex (TPGC) with seven other proteins. We recently identified TBC1D19, a protein of
unknown function, as a novel component of TPGC. TBC1D19 may be an enzyme, as it has a TBC domain,
which shares homology to GTP-activating protein (GAP) domains. We generated a knock-out of TBC1D19 in
mammalian cells and observed a number of novel and exciting phenotypes, including loss of ciliation and
changes in Golgi size and morphology. We will investigate whether these phenotypes can be ascribed to
defects in poly-glutamylation, loss of GAP function, or an unknown activity. These findings suggest a
potentially wider role for TBC1D19 and the TPGC that links microtubule poly-glutamylation with vesicle
trafficking, organelle morphology, and microtubule dynamics. This research will ultimately further our
understanding of microtubules and ciliation in development and disease.

## Key facts

- **NIH application ID:** 10997705
- **Project number:** 1F31GM156062-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Loren Collado
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997705

## Citation

> US National Institutes of Health, RePORTER application 10997705, Investigating the role of TBC1D19 in microtubule dynamics, ciliation and organelle morphology (1F31GM156062-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10997705. Licensed CC0.

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