# Mechanical Regulation of Apical and Invasive Growth

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2020 · $311,000

## Abstract

The goal of this project is to elucidate the mechanisms for feedback regulation of the tip growth-signaling
machinery by mechanical stresses resulting from rapid and invasive growth of tip-growing cells and the roles of
mechanical feedback regulation in enabling these cells to invade tissues. Fast tip growth is vital for cells to
explore the environment or reach distant destinations via guided and invasive growth, e.g., fungal pathogens
invade host tissue and pollen tubes (PT) travel through female tissues to deliver sperms. Fast tip growth
requires efficient tip-targeted exocytosis and tightly regulated relaxation of the apical wall inflated by high
internal turgor pressure (>1 mPa). Little is known about how the tip-growing cells regulate the local relaxation
of the apical wall to generate forces for rapid and invasive growth while maintaining the cell wall integrity
(CWI). To address this fundamental question, the PI established Arabidopsis PT as a model system. The PI
discovered a signaling network that is controlled by the ROP1 Rho-family GTPase, modulates apical
exocytosis, and self-regulates ROP1 via autocrine signaling to promote tip growth. Under the prior R01 grant,
modeling was integrated with experimentation to uncover an exocytosis-coordinated design principle for the
regulation of tip growth. ROP1-dependent exocytosis was shown to orchestrate spatial regulation of ROP1 and
wall mechanics to control tip growth and guidance. A microfluidic device-based tip-chip assay was developed
to study invasive growth. Acute tensile stress resulting from invasive growth was shown to activate ROP1 via
the CUP1 putative mechanosensor specifically required for maintaining CWI in PT experiencing acute stress.
In contrast, CUP1 homolog, ANX, is vital for in vitro CWI likely by sensing gradual tensile stress in PT grown in
vitro. This renewal resubmission will test the hypothesis that CUP1 and ANX sense acute and gradual tensile
stresses respectively, which feedback regulate ROP1 signaling machinery to balance growth with CWI for
efficient apical and invasive growth. Aim 1 will characterize the mechanosensory functions of CUP1 and ANX
by integrating genetic and biochemical studies with single molecule mechanosensing and tip-chip assays. Aim
2 will investigate how mechanosensation by CUP1 cooperates with its sensing of a RALF peptide to achieve
an acute CWI response during invasive growth. Aim 3, by using iterative modeling and experimentation, will
investigate how ROP1 signaling dynamically balances the wall relaxation with maintenance of CWI, and how
this balance allows the tip-growing cells to invade tissues. The project will advance the concept that the
exocytosis-coordinated Rho signaling overarches fast tip growth, guidance and invasive growth, and will
provide unprecedented insights into the mechanisms behind invasive growth, a process essential for cancer
progression and host invasion by fungal pathogens. With conserved Rho signaling underlying t...

## Key facts

- **NIH application ID:** 10003295
- **Project number:** 5R01GM100130-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Yongtao Cui
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $311,000
- **Award type:** 5
- **Project period:** 2012-02-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003295

## Citation

> US National Institutes of Health, RePORTER application 10003295, Mechanical Regulation of Apical and Invasive Growth (5R01GM100130-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10003295. Licensed CC0.

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