ArticleThe Journal of biological chemistry2015
Uncleaved ApoM signal peptide is required for formation of large ApoM/sphingosine 1-phosphate (S1P)-enriched HDL particles.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Review
- Focusing on the Apolipoprotein M-Mitophagy Axis: A Mechanism for Renal Protection in Diabetic Nephropathy.Journal of diabetes research · 2026Review
- Mechanisms of high-density lipoprotein in regulating blood-brain barrier function: insights and implications.Fluids and barriers of the CNS · 2025Review
- Signal Peptides: From Molecular Mechanisms to Applications in Protein and Vaccine Engineering.Biomolecules · 2025Review
- Regulatory role of S1P and its receptors in sepsis-induced liver injury.Frontiers in immunology · 2025Review
- Membrane RRM2-positive cells represent a malignant population with cancer stem cell features in intrahepatic cholangiocarcinoma.Journal of experimental & clinical cancer research : CR · 2024Article
- SARS-CoV-2 induced HDL dysfunction may affect the host's response to and recovery from COVID-19.Immunity, inflammation and disease · 2023Review
- Apolipoprotein M and Sphingosine-1-Phosphate Receptor 1 Promote the Transendothelial Transport of High-Density Lipoprotein.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Good Cholesterol Gone Bad? HDL and COVID-19.International journal of molecular sciences · 2021Review
- The apoM/S1P Complex-A Mediator in Kidney Biology and Disease?Frontiers in medicine · 2021Review
- AIBP, Angiogenesis, Hematopoiesis, and Atherogenesis.Current atherosclerosis reports · 2020Review
- LncRNA TUG1 regulates ApoM to promote atherosclerosis progression through miR-92a/FXR1 axis.Journal of cellular and molecular medicine · 2020Article
- A Chimeric Signal Peptide-Galectin-3 Conjugate Induces Glycosylation-Dependent Cancer Cell-Specific Apoptosis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Abrogation of Endogenous Glycolipid Antigen Presentation on Myelin-Laden Macrophages by D-Sphingosine Ameliorates the Pathogenesis of Experimental Autoimmune Encephalomyelitis.Frontiers in immunology · 2019Article
- Sphingosine 1-Phosphate and Atherosclerosis.Journal of atherosclerosis and thrombosis · 2018Review
- Sphingosine kinase and sphingosine-1-phosphate in liver pathobiology.Critical reviews in biochemistry and molecular biology · 2017Review
- A Novel Perspective on the ApoM-S1P Axis, Highlighting the Metabolism of ApoM and Its Role in Liver Fibrosis and Neuroinflammation.International journal of molecular sciences · 2017Review
- HDL-associated ApoM is anti-apoptotic by delivering sphingosine 1-phosphate to S1P1 & S1P3 receptors on vascular endothelium.Lipids in health and disease · 2017Article
- The roles of bile acids and sphingosine-1-phosphate signaling in the hepatobiliary diseases.Journal of lipid research · 2016Review
- Binding Characteristics of Sphingosine-1-Phosphate to ApoM hints to Assisted Release Mechanism via the ApoM Calyx-Opening.Scientific reports · 2016Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Apolipoprotein M (apoM), a plasma sphingosine 1-phosphate (S1P) carrier, associates with plasma HDL via its uncleaved signal peptide. Hepatocyte-specific apoM overexpression in mice stimulates formation of both larger nascent HDL in hepatocytes and larger mature apoM/S1P-enriched HDL particles in plasma by enhancing hepatic S1P synthesis and secretion. Mutagenesis of apoM glutamine 22 to alanine (apoM(Q22A)) introduces a functional signal peptidase cleavage site. Expression of apoM(Q22A) in ABCA1-expressing HEK293 cells resulted in the formation of smaller nascent HDL particles compared with wild type apoM (apoM(WT)). When apoM(Q22A) was expressed in vivo, using recombinant adenoviruses, smaller plasma HDL particles and decreased plasma S1P and apoM were observed relative to expression of apoM(WT). Hepatocytes isolated from both apoM(WT)- and apoM(Q22A)-expressing mice displayed an equivalent increase in cellular levels of S1P, relative to LacZ controls; however, relative to apoM(WT), apoM(Q22A) hepatocytes displayed more rapid apoM and S1P secretion but minimal apoM(Q22A) bound to nascent lipoproteins. Pharmacologic inhibition of ceramide synthesis increased cellular sphingosine and S1P but not medium S1P in both apoM(WT) and apoM(Q22A) hepatocytes. We conclude that apoM secretion is rate-limiting for hepatocyte S1P secretion and that its uncleaved signal peptide delays apoM trafficking out of the cell, promoting formation of larger nascent apoM- and S1P-enriched HDL particles that are probably precursors of larger apoM/S1P-enriched plasma HDL.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.