PI(4,5)P2 and L-type Ca(2+) Channels Partner Up to Fine-Tune Ca(2+) Dynamics in β Cells

Byung-Chang Suh1, Jun-Hee Yeon1, Cheon-Gyu Park1

  • 1Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea.

Cell Chemical Biology
|July 23, 2016
PubMed

Insights

Researchers used optogenetics to control plasma membrane phosphoinositide levels. Acute changes in phosphoinositide diphosphate (PI(4,5)P2) were shown to impact intracellular calcium and insulin secretion in pancreatic cells.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Physiology

Background:

  • Plasma membrane phosphoinositide diphosphate (PI(4,5)P2) levels are crucial for cellular functions.
  • PI(4,5)P2 is dynamically regulated by cellular energy (ATP) and signaling pathways.
  • Dysregulation of PI(4,5)P2 is implicated in various cellular processes and diseases.

Purpose of the Study:

  • To investigate the direct impact of acute PI(4,5)P2 manipulation on cellular functions.
  • To explore the relationship between PI(4,5)P2 dynamics and intracellular calcium signaling.
  • To determine the effect of altered PI(4,5)P2 on insulin secretion in pancreatic beta cells.

Main Methods:

  • Utilized optogenetics for precise spatiotemporal control of membrane PI(4,5)P2 levels.
  • Employed advanced microscopy techniques to monitor intracellular calcium dynamics.
  • Measured insulin secretion in response to PI(4,5)P2 perturbations.

Main Results:

  • Demonstrated that acute reduction of PI(4,5)P2 levels significantly alters intracellular calcium (Ca2+) dynamics.
  • Showcased a direct correlation between manipulated PI(4,5)P2 and changes in insulin secretion.
  • Optogenetic control provides a novel tool to study rapid lipid signaling events.

Conclusions:

  • Acute changes in membrane PI(4,5)P2 levels have profound effects on calcium signaling and insulin release.
  • Optogenetics offers a powerful method for dissecting the functional roles of membrane lipids in real-time.
  • Findings provide new insights into the regulation of pancreatic beta cell function and potential therapeutic targets.

Related Concept Videos

Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
4.1K
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,...
6.9K
Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
7.3K
The Role of Ion Channels in Neuronal Computation01:19

The Role of Ion Channels in Neuronal Computation

A postsynaptic neuron usually receives numerous impulses from several other presynaptic neurons. The axon hillock of the postsynaptic neuron integrates all these signals and determines the likelihood of firing an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
4.2K
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
6.7K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
3.0K