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The Rho Family- key regulators of the actin cytoskeleton
The rho family are small GTPase monomeric proteins that act as molecular switches that
turn on or off signal transduction pathways in response to chemical or mechanism stimuli.
Rho family proteins exist in the GDP form, the GDP is exchanged for GTP which switches on
the molecule. The receptor responds to different signals but has the same switching
mechanism inside the cells.
Effect of GTPase activation – this changes the activity of the G proteins and increases their
activity.
The Rho protein family of small GTPases has grown to include 20 separate proteins divided
into seven subfamilies, some of these proteins include:
o Control – fibre blast cell.
o Dominant active rho –straight structures, that control the formation of stress fibres.
o Dominant active rac – actin all around the leading edge.
o Dominant active cdc42 – filopodia spikes around the cell.
You can determine the type of switches from the formation of the structure. Rho activates
formin function – this builds the stress fibres and straight structures. For example: Wound
healing assay.
o Dominant negative Rh
o Dominant negative rac
o Dominant negative cdc42
o Dominant negative rho
All of these promote neurite outgrowth and migration of the cell.
Integration of signalling to promote motility.
1) Cdc42 regulates actin polymerisation through its binding to the N-WASP protein.
2) This activates the Arp2/3 complex.
3) Then at the back of the leading edge we have this rho activating leading to myosin 2
activation.
Summary for signal induced changes in the actin cytoskeleton
The Rho protein activates the cdc42 and rac GTP triggers the filopodia and lamellipodia
formation.
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