Related Experiment Video

Updated: Jan 24, 2026

In Vitro Polymerization of F-actin on Early Endosomes
12:15

In Vitro Polymerization of F-actin on Early Endosomes

Published on: August 28, 2017

9.6K

PTEN reduces endosomal PtdIns(4,5)P2 in a phosphatase-independent manner via a PLC pathway

Virginie E Mondin1, Khaled Ben El Kadhi1, Clothilde Cauvin2,3

  • 1Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Canada.

The Journal of Cell Biology
|May 24, 2019
PubMed

Insights

The tumor suppressor PTEN unexpectedly reduces endosomal phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) levels via phospholipase C, independent of its phosphatase activity. This pathway offers a potential therapeutic strategy for Lowe syndrome.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Genetics

Background:

  • The tumor suppressor PTEN normally dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to PtdIns(4,5)P2.
  • Loss of OCRL1, the human orthologue of dOCRL, causes oculocerebrorenal Lowe syndrome, characterized by PtdIns(4,5)P2 accumulation and cytokinesis defects.

Purpose of the Study:

  • To investigate a novel function of PTEN in regulating endosomal PtdIns(4,5)P2 levels.
  • To identify potential therapeutic targets for Lowe syndrome.

Main Methods:

  • Utilized *Drosophila melanogaster* as a model organism.
  • Investigated the enzymatic activity of dPLCXD and its interaction with PTEN.
  • Examined the effects of PTEN and dPLCXD overexpression on PtdIns(4,5)P2 levels and cytokinesis.
  • Tested chemical activation of the pathway in human Lowe syndrome cells and a zebrafish model.

Main Results:

  • Discovered PTEN reduces endosomal PtdIns(4,5)P2 independently of its phosphatase activity.
  • Identified dPLCXD, an atypical phospholipase C, as essential for this PTEN function.
  • Demonstrated that the PTEN/dPLCXD pathway compensates for dOCRL depletion.
  • Showed PTEN or dPLCXD overexpression prevents PtdIns(4,5)P2 accumulation and cytokinesis defects.
  • Found chemical activation of this pathway restored normal cytokinesis in human cells and rescued zebrafish phenotypes.

Conclusions:

  • Identified a novel PTEN/dPLCXD pathway regulating endosomal PtdIns(4,5)P2 levels.
  • This pathway provides a potential new therapeutic strategy for Lowe syndrome by targeting PtdIns(4,5)P2 accumulation and associated defects.

More Related Videos

The Microscopy-Based Assay to Study and Analyze the Recycling Endosomes using SNARE Trafficking08:51

The Microscopy-Based Assay to Study and Analyze the Recycling Endosomes using SNARE Trafficking

Published on: February 12, 2022

4.0K
Nanogold Labeling of the Yeast Endosomal System for Ultrastructural Analyses09:49

Nanogold Labeling of the Yeast Endosomal System for Ultrastructural Analyses

Published on: July 14, 2014

10.7K

Related Concept Videos

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.0K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

4.4K
Maturation of Endosomes01:28

Maturation of Endosomes

The early endosome containing internalized molecules matures through transformations in its location, morphology, intraluminal pH, and membrane protein composition. Together, these changes result in a more acidic late endosome that contains multiple intraluminal vesicles; therefore, the late endosome is also called a multivesicular body (MVB).
Changes in location
The maturing endosome moves along microtubules from the periphery of the cell towards the perinuclear region. This movement of the...
5.7K
Introduction to Test of Independence01:21

Introduction to Test of Independence

In statistics, the term independence means that one can directly obtain the probability of any event involving both variables by multiplying their individual probabilities. Tests of independence are chi-square tests involving the use of a contingency table of observed (data) values.
The test statistic for a test of independence is similar to that of a goodness-of-fit test:
2.9K
Hypothesis Test for Test of Independence01:16

Hypothesis Test for Test of Independence

The test of independence is a chi-square-based test used to determine whether two variables or factors are independent or dependent. This hypothesis test is used to examine the independence of the variables. One can construct two qualitative survey questions or experiments based on the variables in a contingency table. The goal is to see if the two variables are unrelated (independent) or related (dependent). The null and alternative hypotheses for this test are:
H0: The two variables (factors)...
7.4K
The Early Endosome: Endocytosis of Transferrin01:28

The Early Endosome: Endocytosis of Transferrin

Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
4.7K