# Structure and Function of Paxillin

> **NIH NIH R35** · UPSTATE MEDICAL UNIVERSITY · 2021 · $405,000

## Abstract

PROJECT SUMMARY
The broad ongoing objective of this research program is to gain a deeper understanding of the
fundamental mechanisms by which the focal adhesion adaptor/scaffold proteins paxillin and Hic-5
contribute to cell-matrix signaling and thereby control of cell polarity and migration in development and
disease. Importantly, communication between the three elements of the cytoskeleton, the trafficking
machinery and cell-matrix interactions is essential for establishing both apical-basal and front-rear
migration polarity. However, our understanding of the key mechanisms coordinating and integrating
these processes remains incomplete. Through our development of new paxillin and Hic-5 knock out
mouse models, in combination with the use of various ex-vivo 1D, 2D and 3D cell matrix and organoid
model systems and real time imaging approaches, we have identified new roles for paxillin in
establishing epithelial and mesenchymal cell polarity, including regulation of centrosome and Golgi
organization and microtubule stability via control of HDAC6 activity. We have also identified Hic-5 as a
new mediator of F-actin-intermediate filament cross talk, mechanobiology and 3D extracellular matrix
deposition and remodeling. Using these model systems in conjunction with quantitative real time
confocal, light sheet and super resolution imaging approaches, the main goals that we will address in the
upcoming funding period are- Goal 1: How does paxillin contribute to the regulation of polarized
trafficking in directed mesenchymal cell migration? Goal 2: What is the role of paxillin in establishment of
apical-basal polarity and in branching morphogenesis in mammary epithelial cells and Goal 3: How does
Hic-5 regulate the vimentin intermediate filament cytoskeleton organization and function in motile cells
and during epithelial-mesenchymal transition? Through the elucidation of these mechanisms we will be
better positioned to develop rational approaches to disease intervention and to appreciate the basis of
developmental disorders.

## Key facts

- **NIH application ID:** 10135694
- **Project number:** 5R35GM131709-03
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** Christopher E Turner
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $405,000
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135694

## Citation

> US National Institutes of Health, RePORTER application 10135694, Structure and Function of Paxillin (5R35GM131709-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10135694. Licensed CC0.

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