# ACTIN CABLE FORMATION COORDINATED BY APC, FORMINS AND MICROTUBULES IN ANIMAL DEVELOPMENT

> **NIH NIH R01** · CARNEGIE-MELLON UNIVERSITY · 2020 · $291,668

## Abstract

Project Summary
The goal of this proposal is to define the mechanisms controlling dynamic assembly and function of cellular
actin structures in a living, developing animal. Recent advances in single molecule in vitro TIRF microscopy
have made major contributions to our understanding of the molecular mechanisms controlling actin and
microtubule rearrangements. However, the field is lagging behind in the integration of these in vitro
mechanisms into a physiological context by testing them in animal models. To fill this gap, we will use a
combined `top-down' and `bottom-up' strategy, bringing together the genetic and live imaging power of
Drosophila with quantitative in vitro reconstitution and single molecule analysis. Specifically, we focus on a
group of interacting actin assembly factors, which includes Adenomatous polyposis coli proteins 1 and 2
(APC1 and APC2) and the formin Diaphanous (Dia), and how they work together to build a striking array of
long actin cables in Drosophila nurse cells at a specific stage of oogenesis. Our central hypothesis is that
APC1, APC2, and Dia each make a mechanistically distinct and essential contribution to actin cable formation,
and that the proper spatial and temporal pattern of cable assembly arises from these proteins working in
concert under tight regulation by interactions with microtubules and microtubule-associated proteins (e.g., EB1
and CLIP-170), and regulated by GSK3ß kinase. By directly visualizing these mechanisms at the single
molecule level in vitro, and using this information to guide rigorous multi-faceted tests in living Drosophila
ovaries, we will arrive at an unprecedented level of mechanistic understanding of actin assembly and
microtubule-actin cross-talk in the living animal. The specific aims are: (1) Determine how actin cable arrays
are assembled during oogenesis by tightly controlled multi-component mechanisms involving collaborative
actin filament nucleation and elongation factors; and (2) Define the mechanisms by which microtubules trigger
actin cable emergence and interact with growing cables to guide their morphogenesis and their contact with
the nucleus.

## Key facts

- **NIH application ID:** 9923672
- **Project number:** 5R01GM120378-04
- **Recipient organization:** CARNEGIE-MELLON UNIVERSITY
- **Principal Investigator:** BROOKE M MCCARTNEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $291,668
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923672

## Citation

> US National Institutes of Health, RePORTER application 9923672, ACTIN CABLE FORMATION COORDINATED BY APC, FORMINS AND MICROTUBULES IN ANIMAL DEVELOPMENT (5R01GM120378-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9923672. Licensed CC0.

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