# Mechanisms of non-centrosomal microtubule-organizing center functions

> **NIH NIH R01** · FLORIDA STATE UNIVERSITY · 2021 · $347,433

## Abstract

Centrosomes are the major and best-understood microtubule-organizing centers
(MTOCs) in animal cells, yet in most differentiated cells non-centrosomal MTOCs
(ncMTOCs) redirect MT organization instead of the centrosome. The sheer
diversity of ncMTOCs reflects the different functions of various cell types and the
subcellular locations and mechanisms of MT assembly that serve those roles.
Understanding the molecular architecture of these ncMTOCs, the mechanisms of
MT assembly they employ, and the functions they serve to the diverse cell types
they serve remains an important frontier in cell biology and disease. The few
ncMTOCs that have been deciphered reveal architectures and mechanisms of
MT assembly as diverse as the functions they serve for the varied cell types. In
this proposal we expand on a project to define the functions of a perinuclear
ncMTOC in fat body cells which serves the cell by providing nuclear positioning
and is essential for retrograde endosomal trafficking to support the vital secretory
roles of this cell type. We will determine the unique molecular mechanisms of MT
assembly by two distinct protein complexes that control MT assembly/nucleation
from this ncMTOC. Specifically, this proposal aims to further define the structure
of the fat body ncMTOC on the nuclear surface, and to define the mechanisms of
MT assembly by Patronin and Ninein and how they cooperate with the
microtubule polymerase Minispindles (Msps) and other partners to nucleate MTs.
The outcomes of this project will be a definitive and novel understanding of the
molecular and physiological functions of the fat body ncMTOC, revealing
potentially novel disease etiologies for the proteins involved and the processes
that they regulate. Moreover, as a molecular MT nucleation paradigm that is
independent of the widespread microtubule nucleator gamma-tubulin, we will
define at least one new mechanism to generate MTs at MTOCs.

## Key facts

- **NIH application ID:** 10100056
- **Project number:** 1R01GM139971-01
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** TIMOTHY L MEGRAW
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $347,433
- **Award type:** 1
- **Project period:** 2021-03-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10100056

## Citation

> US National Institutes of Health, RePORTER application 10100056, Mechanisms of non-centrosomal microtubule-organizing center functions (1R01GM139971-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10100056. Licensed CC0.

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