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Directional motility induced by epidermal growth factor requires Cdc42
Jeffrey Chou1, Nancy A Burke, Akihiro Iwabu
1Department of Pathology, 713 Scaife, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Experimental Cell Research
|June 12, 2003
Summary
Cellular movement relies on signaling. Cdc42 protein controls cell polarity by directing Phospholipase C-gamma (PLCgamma) to the cell front, influencing cell migration.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cell motility is crucial for biological processes and involves complex intracellular signaling pathways.
- Phospholipase C-gamma (PLCgamma) is vital for lamellipodial protrusion, while Cdc42 regulates filopodium formation and cell polarity.
Purpose of the Study:
- To investigate the potential link between Cdc42 and PLCgamma in controlling cell directionality and motility.
- To understand how Cdc42 influences the localization and activity of PLCgamma during cell migration.
Main Methods:
- Overexpression of different forms of Cdc42 (constitutively active, dominant negative, GFP-tagged) in NR6 fibroblasts.
- Stimulation of cells with epidermal growth factor (EGF) to induce cell migration.
- Microscopic analysis of cell protrusions, Cdc42 localization, and PLCgamma activity at the leading edge.
Main Results:
- Overexpression of Cdc42 disrupted cell directionality, leading to random protrusions and loss of productive motility.
- Epidermal growth factor (EGF) stimulation caused transient localization of GFP-tagged Cdc42 at protrusion edges.
- Active, tyrosyl-phosphorylated PLCgamma accumulated at the cell front, co-localizing with phosphatidylinositol (4,5)-bisphosphate (PIP(2)) hydrolysis.
- Cdc42 and PLCgamma associated in an EGF-dependent manner, suggesting Cdc42 directs PLCgamma to the cell front.
Conclusions:
- Cdc42 plays a critical role in establishing cell polarity during migration.
- Cdc42 likely controls cell polarity, at least partly, by binding to and directing active PLCgamma to the cell's leading edge.
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