# Investigating the establishment, structure, and function of microtubule organizing centers in differentiated cells in vivo

> **NIH NIH R01** · STANFORD UNIVERSITY · 2022 · $315,400

## Abstract

PROJECT SUMMARY/ABSTRACT
The microtubule cytoskeleton is a critical regulator of cell differentiation, and must be spatially organized in
order to fulfill its cellular functions. Although the concept that microtubules are organized by specific sites
called microtubule organizing centers (MTOCs) has been appreciated for more than 50 years, the vast majority
of research on MTOCs has focused on the centrosome. While all animal cells use centrosomes as MTOCs
during mitosis, MTOC function is reassigned to non-centrosomal sites during cell differentiation. For example,
non-centrosomal MTOCs (ncMTOCs) form at the apical membrane of epithelial cells, down the length of axons
and dendrites in neurons, and at the nuclear envelope in myotubes and microtubules are critical for
neurogenesis, muscle function, and in morphogenesis and polarization of most tissues including the heart,
brain, and intestine. Despite their ubiquity and importance in differentiated cells in vivo, little is known about
mechanisms of ncMTOC establishment or the identity of ncMTOC components in an organism, in part due to
the lack of an appropriate genetic model. This proposal tests the central hypothesis that ncMTOCs are
composed of site-specific adapters and microtubule minus end proteins, with adapters linking microtubules
through their minus ends to polarity complexes that mark cellular locations. Our aims will address the
composition and mechanisms of establishment of ncMTOCs, the two significant knowledge gaps in this field
using cutting edge genetic and proteomic tools in the model organism C. elegans. We identified interactors
with the exclusive ncMTOC component PTRN-1/Patronin and will uncover the role of these conserved
interactors in ncMTOC establishment (Aim 1). We will identify novel ncMTOC components using our recently
adapted proximity labeling technique TurboID, applied for the first time in C. elegans, and a high throughput
tissue- and pathway-specific forward genetic screening strategy (Aim 2). Finally, we will test specific models for
ncMTOC establishment using a tissue specific degradation strategy that we have optimized (Aim 3). Proper
microtubule organization is essential for normal development and cell function and hyperactive MTOC function
at the centrosome is a hallmark of some cancers. Thus, the molecules uncovered in these studies could
provide potential therapeutic targets as well as shed light on an important, but understudied topic in cell and
developmental biology.

## Key facts

- **NIH application ID:** 10405583
- **Project number:** 5R01GM133950-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jessica Lynn Feldman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $315,400
- **Award type:** 5
- **Project period:** 2020-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405583

## Citation

> US National Institutes of Health, RePORTER application 10405583, Investigating the establishment, structure, and function of microtubule organizing centers in differentiated cells in vivo (5R01GM133950-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10405583. Licensed CC0.

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