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Updated: Aug 17, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling
T Tominaga1, E Sahai, P Chardin
1University of California, San Francisco Cancer Center 94115, USA.
Abstract:
We have examined the role of the mouse Diaphanous-related formin (DRF) Rho GTPase binding proteins, mDia1 and mDia2, in cell regulation. The DRFs are required for cytokinesis, stress fiber formation, and transcriptional activation of the serum response factor (SRF). 'Activated' mDia1 and mDia2 variants, lacking their GTPase binding domains, cooperated with Rho-kinase or ROCK to form stress fibers but independently activated SRF. Src tyrosine kinase associated and co-localized with the DRFs in endosomes and in mid-bodies of dividing cells. Inhibition of Src also blocked cytokinesis, SRF induction by activated DRFs, and cooperative stress fiber formation with active ROCK. Our results show that the DRF proteins couple Rho and Src during signaling and the regulation of actin dynamics.
Insights
Mouse Diaphanous-related formins (DRFs) like mDia1 and mDia2 are crucial for cell division and stress fiber formation. These proteins link Rho and Src signaling pathways, regulating cell structure and gene expression.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Diaphanous-related formins (DRFs) are key regulators of the actin cytoskeleton.
- DRFs are known to be involved in cell division and stress fiber formation.
- The precise upstream regulators and signaling pathways involving DRFs are not fully understood.
Purpose of the Study:
- To investigate the role of mouse DRFs, specifically mDia1 and mDia2, in cell regulation.
- To elucidate the relationship between DRFs, Rho-kinase (ROCK), and Src tyrosine kinase in cellular processes.
- To understand how DRFs integrate signals from Rho and Src.
Main Methods:
- Utilized 'activated' variants of mDia1 and mDia2 lacking GTPase binding domains.
- Co-expressed DRFs with Rho-kinase (ROCK) to study stress fiber formation.
- Investigated the association and co-localization of Src tyrosine kinase with DRFs.
- Assessed the impact of Src inhibition on DRF-mediated cellular processes.
Main Results:
- Activated mDia1 and mDia2 cooperated with ROCK for stress fiber formation but activated SRF independently.
- Src tyrosine kinase associated with and co-localized with DRFs in endosomes and mid-bodies.
- Src inhibition blocked cytokinesis, SRF induction by activated DRFs, and stress fiber formation with ROCK.
Conclusions:
- DRF proteins act as crucial coupling factors between Rho and Src signaling pathways.
- DRFs play a significant role in regulating actin dynamics and cell division.
- The interplay between DRFs, Rho, and Src is essential for coordinated cellular signaling and function.
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