ArticlePLoS genetics2020
A point mutation decouples the lipid transfer activities of microsomal triglyceride transfer protein.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
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- Directly Measuring Atherogenic Lipoprotein Kinetics in Zebrafish With the Photoconvertible LipoTimer Reporter.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Human hepatoma Huh-7 cell culture models deficient in apolipoprotein B secretion.Journal of lipid research · 2025Article
- Creb3l3 deficiency promotes intestinal lipid accumulation and alters ApoB-containing lipoprotein kinetics.Journal of lipid research · 2025Article
- Phenotype to genotype: A new and rapid approach using whole-genome sequencing.PLoS genetics · 2025Article
- Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes.Nature communications · 2025Article
- Network Pharmacology and Molecular Docking Approach to Identify and Investigate the Mechanisms of Active Components of Areca Catechu in Relation to Gut Disorders.Acta informatica medica : AIM : journal of the Society for Medical Informatics of Bosnia & Herzegovina : casopis Drustva za medicinsku informatiku BiH · 2025Article
- Zebrafish are resilient to the loss of major diacylglycerol acyltransferase enzymes.The Journal of biological chemistry · 2024Article
- Intestinal DHA-PA-PG axis promotes digestive organ expansion by mediating usage of maternally deposited yolk lipids.Nature communications · 2024Article
- A high-cholesterol zebrafish diet promotes hypercholesterolemia and fasting-associated liver steatosis.Journal of lipid research · 2024Article
- Zebrafish ApoB-Containing Lipoprotein Metabolism: A Closer Look.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Pla2g12b drives expansion of triglyceride-rich lipoproteins.Nature communications · 2024Article
- Genome-Wide Association (GWAS) Applied to Carcass and Meat Traits of Nellore Cattle.Metabolites · 2023Article
- Drosophila embryos allocate lipid droplets to specific lineages to ensure punctual development and redox homeostasis.PLoS genetics · 2023Article
- From worms to humans: Understanding intestinal lipid metabolism via model organisms.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023Review
- Article
- Origin, form and function of extraembryonic structures in teleost fishes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Apolipoprotein B-containing lipoproteins (B-lps) are essential for the transport of hydrophobic dietary and endogenous lipids through the circulation in vertebrates. Zebrafish embryos produce large numbers of B-lps in the yolk syncytial layer (YSL) to move lipids from yolk to growing tissues. Disruptions in B-lp production perturb yolk morphology, readily allowing for visual identification of mutants with altered B-lp metabolism. Here we report the discovery of a missense mutation in microsomal triglyceride transfer protein (Mtp), a protein that is essential for B-lp production. This mutation of a conserved glycine residue to valine (zebrafish G863V, human G865V) reduces B-lp production and results in yolk opacity due to aberrant accumulation of cytoplasmic lipid droplets in the YSL. However, this phenotype is milder than that of the previously reported L475P stalactite (stl) mutation. MTP transfers lipids, including triglycerides and phospholipids, to apolipoprotein B in the ER for B-lp assembly. In vitro lipid transfer assays reveal that while both MTP mutations eliminate triglyceride transfer activity, the G863V mutant protein unexpectedly retains ~80% of phospholipid transfer activity. This residual phospholipid transfer activity of the G863V mttp mutant protein is sufficient to support the secretion of small B-lps, which prevents intestinal fat malabsorption and growth defects observed in the mttpstl/stl mutant zebrafish. Modeling based on the recent crystal structure of the heterodimeric human MTP complex suggests the G865V mutation may block triglyceride entry into the lipid-binding cavity. Together, these data argue that selective inhibition of MTP triglyceride transfer activity may be a feasible therapeutic approach to treat dyslipidemia and provide structural insight for drug design. These data also highlight the power of yolk transport studies to identify proteins critical for B-lp biology.
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