PtdIns(3,4,5)P(3)-dependent and -independent roles for PTEN in the control of cell migration

Nick R Leslie1, Xuesong Yang, C Peter Downes

  • 1Division of Molecular Physiology, University of Dundee, Dundee, DD1 5EH, Scotland, United Kingdom. n.r.leslie@dundee.ac.uk

Current Biology : CB
|January 24, 2007
PubMed
Abstract

Insights

Phosphatase and tensin homolog (PTEN) controls mesoderm cell migration in chick embryos. It regulates epithelial-to-mesenchymal transition (EMT) via protein phosphatase activity and directional movement through lipid phosphatase activity.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Background:

  • Phosphatase and tensin homolog (PTEN) is a tumor suppressor that regulates cell signaling pathways.
  • PTEN has both lipid and protein phosphatase activities, with the latter's role being less understood.
  • PTEN's lipid phosphatase activity suppresses phosphoinositide 3-kinase (PI3K)-dependent signaling.

Purpose of the Study:

  • To investigate the role of PTEN in controlling mesoderm cell migration during gastrulation in chick embryos.
  • To determine the specific phosphatase activities of PTEN involved in cell migration and epithelial-to-mesenchymal transition (EMT).

Main Methods:

  • Overexpression of wild-type PTEN and PTEN mutants in chick embryos.
  • Inhibition of PI3K signaling using specific inhibitors.
  • Analysis of cell migration, EMT, cell polarity, and directional movement of mesoderm cells.

Main Results:

  • PTEN overexpression inhibited EMT in anterior and middle primitive streak mesoderm cells, dependent on its PDZ binding site.
  • A PTEN mutant with only protein phosphatase activity (PTEN G129E) retained the ability to inhibit EMT.
  • Inhibition of PI3K or expression of PTEN mutants lacking PDZ binding sites disrupted cell polarity and directional migration.
  • Reactivated TPTE mutants caused nondirectional cell migration.

Conclusions:

  • PTEN regulates mesoderm cell migration through distinct mechanisms involving both protein and lipid phosphatase activities.
  • Protein phosphatase activity of PTEN is crucial for controlling EMT during gastrulation.
  • Lipid phosphatase activity of PTEN is essential for maintaining cell polarity and directional migration.

Related Concept Videos

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.
Cell Migration01:19

Cell Migration

Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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,...