# A molecular examination of mRNA localization and cell polarization

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2021 · $323,400

## Abstract

A contributing factor to a wide spectrum of diseases is compromised cell polarity. Cells establish polarity by
localizing cargo to distinct cellular sites. Central to this process are the molecular motors and cytoskeletal
filaments such as microtubules and actin. Motors are protein complexes that bind cargo, and as suggested by
their name, utilize energy in the form of ATP hydrolysis to transport cargo to a particular site within the cell. A
fundamental gap in our understanding of this process is the mechanism by which motors are able to recognize
and bind their respective cargo in the complex and crowded environment of the cell. It is generally assumed
that adaptor proteins, by binding directly to cargo and tethering cargo to motor complexes, fulfill this critical
role. However, for most cargo that we know to be actively transported by microtubule motors, the identity of the
adaptor is unknown. The goal of this proposal is to address this gap in knowledge using the Drosophila egg
chamber as a model. The central hypothesis of this application is that Egalitarian (Egl) and Tropomyosin1C
(Tm1C) are cargo adaptors for the Dynein and Kinesin1 motors respectively. Several mRNAs have been
shown to localize within specific regions of the Drosophila oocyte. These include native transcripts such as
oskar, bicoid and gurken as well as transposon mRNAs such as TAHRE and I factor. In Aim1 of this
application, we test the hypothesis that Egl links these mRNAs to Dynein. We also propose to determine the
specific protein interactions that tether the Egl/mRNA complex to the Dynein motor. Over the past decade,
several transposons have been identified that localize within the oocyte. In addition, localization elements from
these transposons are bound by Egl, suggesting that they are linked to motor complexes via this adaptor. In
Aim2 of this application, we hypothesize that oocyte localization represents an adaptive property of
transposons that facilitates their propagation to subsequent generations. We suggest that transposons have
evolved mechanisms to highjack the host localization machinery and we propose a genome-wide analysis to
test this hypothesis. The posterior localization of oskar mRNA requires Kinesin heavy chain (Khc), but not its
canonical adaptor, Kinesin light chain (Klc). In the previous funding cycle, we demonstrated that a novel
isoform of Tropomyosin1, referred to as Tm1C, fulfills this role as the Khc adaptor. In Aim3 of this application,
we propose to define the mechanism by which Tm1C functions in the oskar pathway. Furthermore, our results
suggest that Tm1C is expressed and present in a complex with Khc in somatic tissues. We hypothesize that
this adaptor links additional unknown cargoes with the Kinesin1 motor. Therefore, an additional goal of this aim
is to identify these unknown somatic cargoes bound by Tm1C.

## Key facts

- **NIH application ID:** 10173803
- **Project number:** 5R01GM100088-09
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Graydon Gonsalvez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $323,400
- **Award type:** 5
- **Project period:** 2013-09-30 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10173803

## Citation

> US National Institutes of Health, RePORTER application 10173803, A molecular examination of mRNA localization and cell polarization (5R01GM100088-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10173803. Licensed CC0.

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