GPIHBP1 on oligodendrocytes binds lipoprotein lipase within the human brain
Minjun Liu1, Madison Hung1, Ellen Kozlov1
1Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
Summary
Scientists discovered GPIHBP1 binds to lipoprotein lipase (LPL) in the human brain. This finding suggests GPIHBP1 delivers fatty acids to oligodendrocytes, crucial for brain function and lipid metabolism.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Lipoprotein lipase (LPL) is essential for fatty acid delivery in peripheral tissues, bound by GPIHBP1 on capillary endothelial cells.
- In the central nervous system, LPL's binding site and function remain unclear, despite its synthesis by various brain cells like microglia and oligodendrocyte precursor cells (OPCs).
Purpose of the Study:
- To identify the binding site for interstitial LPL in the human brain.
- To investigate the role of GPIHBP1 in LPL localization and function within the central nervous system.
Main Methods:
- Analysis of single nuclei RNA-sequencing databases from the human brain to assess gene expression.
- In situ hybridization and immunohistochemical staining to confirm protein localization and colocalization.
Main Results:
- The gene GPIHBP1 is expressed in human oligodendrocytes, but not in OPCs, mirroring expression patterns of myelin proteins and lipid-related enzymes.
- GPIHBP1 and LPL were found to be colocalized on oligodendrocytes in the human brain.
- These findings identify GPIHBP1 as the primary binding site for interstitial LPL in the human brain.
Conclusions:
- GPIHBP1 serves as the principal binding site for interstitial LPL in the human brain.
- GPIHBP1-bound LPL likely hydrolyzes interstitial lipids, supplying fatty acids to oligodendrocytes for their metabolic needs.
Related Concept Videos
01:42Phosphoinositides 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...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
01:29GPI Anchoring of Proteins in the ER Membrane
GPI-anchoring is a post-translational, reversible protein modification that is ubiquitous in eukaryotes. Such proteins are primarily present on the exoplasmic leaflet of the plasma membrane.
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
01:11IP3/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...
01:32Lipids as Anchors
In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains the...
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains the...
01:19Formation of Lipopolysaccharides
Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin, triggering...