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Mammalian Cell Division in 3D Matrices via Quantitative Confocal Reflection Microscopy
Published on: November 29, 2017
Cdc42 regulates extracellular matrix remodeling in three dimensions.
Nisha S Sipes1, Yuxin Feng, Fukun Guo
1Division of Experimental Hematology and Cancer Biology, Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA.
The Journal of Biological Chemistry
|September 2, 2011
Summary
The Rho GTPase Cdc42 is crucial for extracellular matrix (ECM) organization in 3D. Cdc42 deficiency impairs cell-matrix interactions, affecting collagen gel contraction and fibronectin organization.
Area of Science:
- Cell Biology
- Biochemistry
- Biophysics
Background:
- Extracellular matrix (ECM) plays a vital role in cell regulation and tumor progression.
- Previous studies on Cdc42's role in cell-ECM interactions used 2D cultures and dominant mutants, potentially causing nonspecific effects.
Purpose of the Study:
- To define the role of Cdc42 signaling pathways in ECM organization using a 3D culture system.
- To investigate the reciprocal interactions between cells and the surrounding matrix.
Main Methods:
- Utilized three-dimensional (3D) culture systems with conditional gene-targeted primary mouse embryonic fibroblasts.
- Assessed global cell-matrix interactions, including collagen gel contraction, focal adhesion complex formation, and fibronectin deposition.
- Investigated the involvement of downstream effectors like p21-activated kinase (PAK), Par6, and WASP.
Main Results:
- Cdc42 deficiency resulted in defective cell-matrix interactions, evidenced by decreased collagen gel contraction and altered cell morphology.
- Reduced focal adhesion complex formation, decreased synthesis and activation of matrix metalloproteinase 9 (MMP9), and altered fibronectin deposition were observed.
- Downstream of Cdc42, p21-activated kinase (PAK) was implicated in regulating collagen gel contraction and fibronectin organization.
Conclusions:
- Cdc42 is essential for ECM remodeling in three dimensions.
- Beyond its known roles in actin organization, proliferation, and vesicle trafficking, Cdc42 significantly influences ECM organization and cell-matrix interactions in a 3D context.
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