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Related Concept Videos

Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

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Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
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Cell Motility through Blebbing01:16

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Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
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The Contractile Ring02:15

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Contractile rings are composed of microfilaments and are responsible for separating the daughter cells during cytokinesis. Contractile ring assembly proceeds along with other cell cycle events; however, very few mechanistic details are known about the timing and coordination of the contractile rings with the cell cycle.
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A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
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Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
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Related Experiment Video

Updated: Jun 14, 2025

Author Spotlight: Optogenetic Inhibition of Rho1-Mediated Actomyosin Contractility Coupled with Measurement of Epithelial Tension in Drosophila Embryos
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Excitable Rho dynamics control cell shape and motility by sequentially activating ERM proteins and actomyosin

Seph Marshall-Burghardt1,2, Rodrigo A Migueles-Ramírez1,3, Qiyao Lin1,2

  • 1Department of Biology, Stewart Biology Building, McGill University, Montréal, Québec H3A 1B1, Canada.

Science Advances
|September 6, 2024
PubMed
Summary

The small GTPase Rho drives cell retraction, not protrusion, by activating ezrin-radixin-moesin proteins for actin-membrane attachment and nonmuscle myosin 2 for contractility during cell migration.

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Last Updated: Jun 14, 2025

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Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein GST-RhoAG17A from Epithelial Cell Lysates
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Area of Science:

  • Cell Biology
  • Biophysics
  • Molecular Biology

Background:

  • Cell migration is essential for development and disease.
  • Cytoskeletal dynamics, including actin-membrane attachment and contractility, regulate cell shape changes during migration.
  • The role of the small GTPase Rho in coordinating these processes has been unclear, with conflicting reports of its activity during protrusion and retraction.

Purpose of the Study:

  • To elucidate the precise role and spatiotemporal regulation of Rho activity during cell migration.
  • To investigate the downstream effectors and mechanisms by which Rho controls cytoskeletal rearrangements.
  • To understand how Rho activity coordinates actin-membrane attachment and contractility for cell shape changes.

Main Methods:

  • Live-cell imaging of Rho activity using fluorescent reporters.
  • Pharmacological inhibition of Rho-associated kinases (SLK/LOK).
  • Analysis of cytoskeletal dynamics, including actin-membrane attachment (ERM proteins) and contractility (nonmuscle myosin 2).

Main Results:

  • Rho activity was found to be absent in cell protrusions and active specifically during cell retractions.
  • Rho rapidly activated ezrin-radixin-moesin (ERM) proteins, enhancing actin-membrane attachment.
  • Rho subsequently activated nonmuscle myosin 2 (NM2) with a delay, contributing to contractility, and NM2 acted as a negative feedback regulator.
  • Inhibition of SLK/LOK kinases disrupted ERM activation, impaired Rho-induced contractions, and altered cell morphology.

Conclusions:

  • Rho activity drives cell retractions by sequentially promoting ERM-mediated actin-membrane attachment and NM2-dependent contractility.
  • This study clarifies the spatiotemporal role of Rho in cell migration, highlighting its function in retraction rather than protrusion.
  • The findings reveal a mechanism where Rho coordinates force transmission and cytoskeletal contractility for effective cell movement.