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Müller, G. ; Müller, T.D.

(Patho)physiology of glycosylphosphatidylinositol-anchored proteins II: Intercellular transfer of matter (Inheritance?) that matters.

Biomolecules 13:41 (2023)

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Glycosylphosphatidylinositol (GPI)-anchored proteins (APs) are anchored at the outer leaflet of the plasma membrane (PM) bilayer by covalent linkage to a typical glycolipid and expressed in all eukaryotic organisms so far studied. Lipolytic release from PMs into extracellular compartments and intercellular transfer are regarded as the main (patho)physiological roles exerted by GPI-APs. The intercellular transfer of GPI-APs relies on the complete GPI anchor and is mediated by extracellular vesicles such as microvesicles and exosomes and lipid-free homo- or heteromeric aggregates, and lipoprotein-like particles such as prostasomes and surfactant-like particles, or lipid-containing micelle-like complexes. In mammalian organisms, non-vesicular transfer is controlled by the distance between donor and acceptor cells/tissues; intrinsic conditions such as age, metabolic state, and stress; extrinsic factors such as GPI-binding proteins; hormones such as insulin; and drugs such as anti-diabetic sulfonylureas. It proceeds either “directly” upon close neighborhood or contact of donor and acceptor cells or “indirectly” as a consequence of the induced lipolytic release of GPI-APs from PMs. Those displace from the serum GPI-binding proteins GPI-APs, which have retained the complete anchor, and become assembled in aggregates or micelle-like complexes. Importantly, intercellular transfer of GPI-APs has been shown to induce specific phenotypes such as stimulation of lipid and glycogen synthesis, in cultured human adipocytes, blood cells, and induced pluripotent stem cells. As a consequence, intercellular transfer of GPI-APs should be regarded as non-genetic inheritance of (acquired) features between somatic cells which is based on the biogenesis and transmission of matter such as GPI-APs and “membrane landscapes”, rather than the replication and transmission of information such as DNA. Its operation in mammalian organisms remains to be clarified.

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Publication type Article: Journal article

Document type Review

Corresponding Author

Keywords (g)pi-specific Phospholipase C/d (gpi-plc/d) ; Adipose And Blood Cells ; Diabetes ; Glimepiride ; Glycosylphosphatidylinositol (gpi)-anchored Proteins (gpi-aps) ; Inheritance Of Acquired Features ; Protein And Information Transfer; Paroxysmal-nocturnal Hemoglobinuria; Decay-accelerating Factor; Erythrocyte Anion Transporter; Complement Regulatory Proteins; Variant Surface Glycoprotein; Natural-killer-cells; Red-blood-cells; Rat Adipocytes; Plasma-membrane; Lipid Droplets

ISSN (print) / ISBN 2218-273X

e-ISSN 2218-273X

Journal Biomolecules

Quellenangaben Volume: 13, Issue: 6, Article Number: 41

Publisher MDPI

Publishing Place Basel

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Obesity (IDO)

Grants
European Research Council ERC-CoG Trusted
German Center for Diabetes Research (DZD e.V.)
German Research Foundation (DFG)