Cholesterol Regulation of Membrane Proteins Revealed by Two-Color Super-Resolution Imaging

Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP2) are hydrophobic molecules that regulate protein function in the plasma membrane of all cells. In this review, we discuss how changes in cholesterol concentration cause nanoscopic (<200 nm) movements of membrane proteins to regulate the...

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Published inMembranes (Basel) Vol. 13; no. 2; p. 250
Main Authors Yuan, Zixuan, Hansen, Scott B.
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 01.02.2023
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Abstract Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP2) are hydrophobic molecules that regulate protein function in the plasma membrane of all cells. In this review, we discuss how changes in cholesterol concentration cause nanoscopic (<200 nm) movements of membrane proteins to regulate their function. Cholesterol is known to cluster many membrane proteins (often palmitoylated proteins) with long-chain saturated lipids. Although PIP2 is better known for gating ion channels, in this review, we will discuss a second independent function as a regulator of nanoscopic protein movement that opposes cholesterol clustering. The understanding of the movement of proteins between nanoscopic lipid domains emerged largely through the recent advent of super-resolution imaging and the establishment of two-color techniques to label lipids separate from proteins. We discuss the labeling techniques for imaging, their strengths and weakness, and how they are used to reveal novel mechanisms for an ion channel, transporter, and enzyme function. Among the mechanisms, we describe substrate and ligand presentation and their ability to activate enzymes, gate channels, and transporters rapidly and potently. Finally, we define cholesterol-regulated proteins (CRP) and discuss the role of PIP2 in opposing the regulation of cholesterol, as seen through super-resolution imaging.
AbstractList Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP ) are hydrophobic molecules that regulate protein function in the plasma membrane of all cells. In this review, we discuss how changes in cholesterol concentration cause nanoscopic (<200 nm) movements of membrane proteins to regulate their function. Cholesterol is known to cluster many membrane proteins (often palmitoylated proteins) with long-chain saturated lipids. Although PIP is better known for gating ion channels, in this review, we will discuss a second independent function as a regulator of nanoscopic protein movement that opposes cholesterol clustering. The understanding of the movement of proteins between nanoscopic lipid domains emerged largely through the recent advent of super-resolution imaging and the establishment of two-color techniques to label lipids separate from proteins. We discuss the labeling techniques for imaging, their strengths and weakness, and how they are used to reveal novel mechanisms for an ion channel, transporter, and enzyme function. Among the mechanisms, we describe substrate and ligand presentation and their ability to activate enzymes, gate channels, and transporters rapidly and potently. Finally, we define cholesterol-regulated proteins (CRP) and discuss the role of PIP in opposing the regulation of cholesterol, as seen through super-resolution imaging.
Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP2) are hydrophobic molecules that regulate protein function in the plasma membrane of all cells. In this review, we discuss how changes in cholesterol concentration cause nanoscopic (<200 nm) movements of membrane proteins to regulate their function. Cholesterol is known to cluster many membrane proteins (often palmitoylated proteins) with long-chain saturated lipids. Although PIP2 is better known for gating ion channels, in this review, we will discuss a second independent function as a regulator of nanoscopic protein movement that opposes cholesterol clustering. The understanding of the movement of proteins between nanoscopic lipid domains emerged largely through the recent advent of super-resolution imaging and the establishment of two-color techniques to label lipids separate from proteins. We discuss the labeling techniques for imaging, their strengths and weakness, and how they are used to reveal novel mechanisms for an ion channel, transporter, and enzyme function. Among the mechanisms, we describe substrate and ligand presentation and their ability to activate enzymes, gate channels, and transporters rapidly and potently. Finally, we define cholesterol-regulated proteins (CRP) and discuss the role of PIP2 in opposing the regulation of cholesterol, as seen through super-resolution imaging.Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP2) are hydrophobic molecules that regulate protein function in the plasma membrane of all cells. In this review, we discuss how changes in cholesterol concentration cause nanoscopic (<200 nm) movements of membrane proteins to regulate their function. Cholesterol is known to cluster many membrane proteins (often palmitoylated proteins) with long-chain saturated lipids. Although PIP2 is better known for gating ion channels, in this review, we will discuss a second independent function as a regulator of nanoscopic protein movement that opposes cholesterol clustering. The understanding of the movement of proteins between nanoscopic lipid domains emerged largely through the recent advent of super-resolution imaging and the establishment of two-color techniques to label lipids separate from proteins. We discuss the labeling techniques for imaging, their strengths and weakness, and how they are used to reveal novel mechanisms for an ion channel, transporter, and enzyme function. Among the mechanisms, we describe substrate and ligand presentation and their ability to activate enzymes, gate channels, and transporters rapidly and potently. Finally, we define cholesterol-regulated proteins (CRP) and discuss the role of PIP2 in opposing the regulation of cholesterol, as seen through super-resolution imaging.
Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP2) are hydrophobic molecules that regulate protein function in the plasma membrane of all cells. In this review, we discuss how changes in cholesterol concentration cause nanoscopic (<200 nm) movements of membrane proteins to regulate their function. Cholesterol is known to cluster many membrane proteins (often palmitoylated proteins) with long-chain saturated lipids. Although PIP2 is better known for gating ion channels, in this review, we will discuss a second independent function as a regulator of nanoscopic protein movement that opposes cholesterol clustering. The understanding of the movement of proteins between nanoscopic lipid domains emerged largely through the recent advent of super-resolution imaging and the establishment of two-color techniques to label lipids separate from proteins. We discuss the labeling techniques for imaging, their strengths and weakness, and how they are used to reveal novel mechanisms for an ion channel, transporter, and enzyme function. Among the mechanisms, we describe substrate and ligand presentation and their ability to activate enzymes, gate channels, and transporters rapidly and potently. Finally, we define cholesterol-regulated proteins (CRP) and discuss the role of PIP2 in opposing the regulation of cholesterol, as seen through super-resolution imaging.
Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP 2 ) are hydrophobic molecules that regulate protein function in the plasma membrane of all cells. In this review, we discuss how changes in cholesterol concentration cause nanoscopic (<200 nm) movements of membrane proteins to regulate their function. Cholesterol is known to cluster many membrane proteins (often palmitoylated proteins) with long-chain saturated lipids. Although PIP 2 is better known for gating ion channels, in this review, we will discuss a second independent function as a regulator of nanoscopic protein movement that opposes cholesterol clustering. The understanding of the movement of proteins between nanoscopic lipid domains emerged largely through the recent advent of super-resolution imaging and the establishment of two-color techniques to label lipids separate from proteins. We discuss the labeling techniques for imaging, their strengths and weakness, and how they are used to reveal novel mechanisms for an ion channel, transporter, and enzyme function. Among the mechanisms, we describe substrate and ligand presentation and their ability to activate enzymes, gate channels, and transporters rapidly and potently. Finally, we define cholesterol-regulated proteins (CRP) and discuss the role of PIP 2 in opposing the regulation of cholesterol, as seen through super-resolution imaging.
Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP[sub.2] ) are hydrophobic molecules that regulate protein function in the plasma membrane of all cells. In this review, we discuss how changes in cholesterol concentration cause nanoscopic (<200 nm) movements of membrane proteins to regulate their function. Cholesterol is known to cluster many membrane proteins (often palmitoylated proteins) with long-chain saturated lipids. Although PIP[sub.2] is better known for gating ion channels, in this review, we will discuss a second independent function as a regulator of nanoscopic protein movement that opposes cholesterol clustering. The understanding of the movement of proteins between nanoscopic lipid domains emerged largely through the recent advent of super-resolution imaging and the establishment of two-color techniques to label lipids separate from proteins. We discuss the labeling techniques for imaging, their strengths and weakness, and how they are used to reveal novel mechanisms for an ion channel, transporter, and enzyme function. Among the mechanisms, we describe substrate and ligand presentation and their ability to activate enzymes, gate channels, and transporters rapidly and potently. Finally, we define cholesterol-regulated proteins (CRP) and discuss the role of PIP[sub.2] in opposing the regulation of cholesterol, as seen through super-resolution imaging.
Audience Academic
Author Yuan, Zixuan
Hansen, Scott B.
AuthorAffiliation 3 Skaggs Graduate School of Chemical and Biological Sciences, The Scripps Research Institute, Jupiter, FL 33458, USA
1 Department of Molecular Medicine, Department of Neuroscience, UF Scripps, Jupiter, FL 33458, USA
2 Department of Neuroscience UF Scripps, Jupiter, FL 33458, USA
AuthorAffiliation_xml – name: 1 Department of Molecular Medicine, Department of Neuroscience, UF Scripps, Jupiter, FL 33458, USA
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  orcidid: 0000-0003-0086-9753
  surname: Hansen
  fullname: Hansen, Scott B.
BackLink https://www.ncbi.nlm.nih.gov/pubmed/36837753$$D View this record in MEDLINE/PubMed
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Issue 2
Keywords nanoscopic
clustering
lipid raft
ion channel
PIP2
transporter
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PublicationTitleAlternate Membranes (Basel)
PublicationYear 2023
Publisher MDPI AG
MDPI
Publisher_xml – name: MDPI AG
– name: MDPI
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Snippet Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP2) are hydrophobic molecules that regulate protein function in the plasma membrane of all cells. In...
Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP ) are hydrophobic molecules that regulate protein function in the plasma membrane of all cells. In...
Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP[sub.2] ) are hydrophobic molecules that regulate protein function in the plasma membrane of all...
Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP 2 ) are hydrophobic molecules that regulate protein function in the plasma membrane of all cells....
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StartPage 250
SubjectTerms Alzheimer's disease
Binding sites
Biological control systems
Biological transport
Channel gating
Cholesterol
Cholesterol metabolism
Clustering
Color
Cytokines
Enzymes
Health aspects
Hydrophobicity
Image resolution
Inositol
Inositols
ion channel
Ion channels
Ligands
lipid raft
Lipids
Localization
Medical research
Medicine, Experimental
Membrane lipids
Membrane proteins
Membranes
Microscope and microscopy
nanoscopic
Nanotechnology
Optical properties
Phosphatidylinositol 4,5-diphosphate
Physiological aspects
PIP2
Potassium
Proteins
Review
Substrates
transporter
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Title Cholesterol Regulation of Membrane Proteins Revealed by Two-Color Super-Resolution Imaging
URI https://www.ncbi.nlm.nih.gov/pubmed/36837753
https://www.proquest.com/docview/2779619673
https://www.proquest.com/docview/2780077366
https://pubmed.ncbi.nlm.nih.gov/PMC9966874
https://doaj.org/article/309a41b5f0f640eb84f55119d012991b
Volume 13
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