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Related Concept Videos

Phosphoinositides and PIPs01:42

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...
IP3/DAG Signaling Pathway01:11

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...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Membrane Asymmetry Regulating Transporters01:19

Membrane Asymmetry Regulating Transporters

Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...

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Related Experiment Video

Updated: May 19, 2026

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
08:49

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

Published on: March 14, 2021

A human phospholipid phosphatase activated by a transmembrane control module.

Christian R Halaszovich1, Michael G Leitner, Angeliki Mavrantoni

  • 1Institute of Physiology and Pathophysiology, Philipps-Universität Marburg, 35037 Marburg, Germany.

Journal of Lipid Research
|August 17, 2012
PubMed
Summary

Mammalian voltage-sensitive phosphatases (VSPs) were elusive until now. This study shows human VSP1 (hVSP1) is activated by membrane potential, initiating phosphoinositide signaling.

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Last Updated: May 19, 2026

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
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Published on: March 14, 2021

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A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
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A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors

Published on: April 29, 2022

Area of Science:

  • Biochemistry
  • Cell Biology
  • Neuroscience

Background:

  • Voltage-sensitive phosphatases (VSPs) link membrane potential to intracellular signaling.
  • Mammalian VSP homologs exist, but their function and regulation remain unclear.

Purpose of the Study:

  • To investigate the function and regulation of human VSP1 (hVSP1/TPIP).
  • To determine if mammalian VSPs are controlled by membrane potential.

Main Methods:

  • Engineered a chimeric hVSP1 with enhanced membrane targeting and an invertebrate VSP voltage sensor domain (VSD).
  • Assessed hVSP1's enzymatic activity and substrate specificity.
  • Investigated the role of the endogenous VSD in controlling phosphatase activity.

Main Results:

  • hVSP1 functions as a phosphoinositide-5-phosphatase, primarily acting on PI(4,5)P(2).
  • Enzymatic activity of the chimeric hVSP1 is regulated by membrane potential.
  • The endogenous VSD of hVSP1 acts as an intramolecular switch controlling the phosphatase domain.

Conclusions:

  • Mammalian VSPs, like hVSP1, are voltage-sensitive enzymes.
  • hVSP1 initiates signaling cascades via phosphoinositide hydrolysis in response to membrane depolarization.
  • VSP-mediated phosphoinositide signaling plays a role in mammalian cellular functions.