Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Phosphoinositides and PIPs

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...

Assembly of Signaling Complexes

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...

IP3/DAG Signaling Pathway

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...

PI3K/mTOR/AKT Signaling Pathway

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...

The JAK-STAT Signaling Pathway

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...

Catenins

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

The reliability of biomedical science: A case history of a maturing experimental field.

BioEssays : news and reviews in molecular, cellular and developmental biology·2022

Same author

PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection.

PLoS pathogens·2019

Same author

Do inositol supplements enhance phosphatidylinositol supply and thus support endoplasmic reticulum function?

The British journal of nutrition·2018

Same author

Drug Redeployment to Kill Leukemia and Lymphoma Cells by Disrupting SCD1-Mediated Synthesis of Monounsaturated Fatty Acids.

Cancer research·2015

Same author

Inositol lipids: from an archaeal origin to phosphatidylinositol 3,5-bisphosphate faults in human disease.

The FEBS journal·2013

Same author

Versatility and nuances of the architecture of haematopoiesis - Implications for the nature of leukaemia.

Leukemia research·2011

Search research articles

Related Experiment Video

Updated: Jun 26, 2026

Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation

Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation

Published on: January 6, 2016

A protein complex that regulates PtdIns(3,5)P2 levels.

Robert H Michell¹, Stephen K Dove

¹School of Biosciences, University of Birmingham, Edgbaton, Birmingham, UK. r.h.michell@bham.ac.uk

The EMBO Journal

|January 23, 2009

Summary

Scientists uncovered how cells regulate phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) synthesis. A multiprotein complex controls PtdIns(3,5)P2 production, and mutations cause neurodegeneration.

Area of Science:

Cell Biology
Membrane Trafficking
Neuroscience

Background:

Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) is crucial for retrograde membrane trafficking from late endosomes and lysosomes.
The precise mechanisms regulating PtdIns(3,5)P2 synthesis, particularly in response to cellular stress like hyperosmotic shock, are not fully understood.

Purpose of the Study:

To elucidate the multiprotein complex controlling PtdIns(3,5)P2 synthesis.
To understand how mutations in key components, such as VAC14, affect PtdIns(3,5)P2 production and cellular function.
To investigate the link between impaired PtdIns(3,5)P2 regulation and neurodegenerative conditions.

Main Methods:

Biochemical analysis of the PtdIns(3,5)P2 synthesizing complex.
Genetic studies using VAC14 mutations in a mouse model.

More Related Videos

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Quantitative Detection of DNA-Protein Crosslinks and Their Post-Translational Modifications

Quantitative Detection of DNA-Protein Crosslinks and Their Post-Translational Modifications

Published on: April 21, 2023

Related Experiment Videos

Last Updated: Jun 26, 2026

Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation

Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation

Published on: January 6, 2016

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Quantitative Detection of DNA-Protein Crosslinks and Their Post-Translational Modifications

Quantitative Detection of DNA-Protein Crosslinks and Their Post-Translational Modifications

Published on: April 21, 2023

Analysis of membrane trafficking and PtdIns(3,5)P2 levels in cellular and animal models.

Main Results:

The study identifies a multiprotein complex essential for PtdIns(3,5)P2 synthesis.
A mutation in the scaffold protein VAC14 was shown to functionally impair the complex.
This impairment leads to defects in PtdIns(3,5)P2 production and is linked to neurodegeneration in mice.

Conclusions:

The Weisman group provides a comprehensive model for PtdIns(3,5)P2 synthesis regulation.
Dysfunctional VAC14 disrupts the PtdIns(3,5)P2 synthesizing complex, impacting membrane trafficking.
Impaired PtdIns(3,5)P2 homeostasis due to VAC14 mutations contributes to neurodegenerative pathology.