Related Experiment Video

Updated: Jul 18, 2026

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

Akt-mediated GSK-3beta inhibition prevents migration of polyamine-depleted intestinal epithelial cells via Rac1

R J Vaidya1, R M Ray, L R Johnson

  • 1Department of Physiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA. rvaidya@physio1.utmem.edu

Cellular and Molecular Life Sciences : CMLS
|November 17, 2006
PubMed

Insights

Polyamines are crucial for intestinal epithelial cell migration and wound healing. Depleting polyamines activates Akt, inhibiting cell migration via GSK-3beta and Rac1, hindering wound repair.

Area of Science:

  • Cell Biology
  • Gastroenterology
  • Molecular Biology

Background:

  • Intestinal epithelial cell (IEC) migration is vital for mucosal wound healing.
  • Previous studies indicated polyamine depletion inhibits IEC-6 cell migration.
  • Akt signaling and its target GSK-3beta are known regulators of cell migration.

Purpose of the Study:

  • To investigate the role of elevated phosphatidylinositol 3-kinase (PI3K)/Akt signaling in the migration of polyamine-depleted cells.
  • To elucidate the mechanisms by which polyamine depletion affects IEC migration.

Main Methods:

  • Utilized polyamine-depleted IEC-6 cells.
  • Assessed Akt and GSK-3beta phosphorylation.
  • Employed PI3K inhibitor (LY294002) and GSK-3beta inhibitor (AR-A014418).
  • Analyzed cell migration, Rac1 activation, and actin cytoskeleton structure.

Main Results:

  • Polyamine-depleted cells exhibited increased Akt (Ser473) and GSK-3beta (Ser9) phosphorylation.
  • PI3K inhibition (LY294002) reduced Akt phosphorylation, enhanced migration, activated Rac1, and restored actin structure in depleted cells.
  • GSK-3beta inhibition (AR-A014418) disrupted the actin cytoskeleton and inhibited migration, similar to polyamine depletion.

Conclusions:

  • Sustained Akt activation due to polyamine depletion inhibits intestinal epithelial cell migration.
  • This inhibition occurs through the downstream signaling pathways involving GSK-3beta and Rac1.
  • Restoring PI3K/Akt signaling may offer therapeutic potential for mucosal wound healing.

More Related Videos

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum09:40

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

Published on: September 20, 2011

Comparing the Affinity of GTPase-binding Proteins using Competition Assays10:37

Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Published on: October 8, 2015

Related Concept Videos

Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

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,...
Cell Migration01:09

Cell Migration

Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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.
Three regulatory proteins control their activity:
Cytoskeletal Coordination in Cell Migration01:32

Cytoskeletal Coordination in Cell Migration

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 proteins that...
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists01:23

Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists

Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...