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Status: Bibliographieeintrag

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Verfasst von:Juarez Altuzar, Janathan Michael [VerfasserIn]   i
 Notbohm, Judith [VerfasserIn]   i
 Stein, Frank [VerfasserIn]   i
 Haberkant, Per [VerfasserIn]   i
 Hempelmann, Pia [VerfasserIn]   i
 Heybrock, Saskia [VerfasserIn]   i
 Worsch, Jutta [VerfasserIn]   i
 Saftig, Paul [VerfasserIn]   i
 Höglinger, Doris [VerfasserIn]   i
Titel:Lysosome-targeted multifunctional lipid probes reveal the sterol transporter NPC1 as a sphingosine interactor
Verf.angabe:Janathan Altuzar, Judith Notbohm, Frank Stein, Per Haberkant, Pia Hempelmann, Saskia Heybrock, Jutta Worsch, Paul Saftig, and Doris Höglinger
E-Jahr:2023
Jahr:March 9, 2023
Umfang:12 S.
Illustrationen:Illustrationen
Fussnoten:Gesehen am 26.07.2024
Titel Quelle:Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
Ort Quelle:Washington, DC : National Acad. of Sciences, 1915
Jahr Quelle:2023
Band/Heft Quelle:120(2023), 11, Artikel-ID e2213886120, Seite 1-12
ISSN Quelle:1091-6490
Abstract:Lysosomes are catabolic organelles involved in macromolecular digestion, and their dysfunction is associated with pathologies ranging from lysosomal storage disorders to common neurodegenerative diseases, many of which have lipid accumulation phenotypes. The mechanism of lipid efflux from lysosomes is well understood for cholesterol, while the export of other lipids, particularly sphingosine, is less well studied. To overcome this knowledge gap, we have developed functionalized sphingosine and cholesterol probes that allow us to follow their metabolism, protein interactions, and their subcellular localization. These probes feature a modified cage group for lysosomal targeting and controlled release of the active lipids with high temporal precision. An additional photocrosslinkable group allowed for the discovery of lysosomal interactors for both sphingosine and cholesterol. In this way, we found that two lysosomal cholesterol transporters, NPC1 and to a lesser extent LIMP-2/SCARB2, bind to sphingosine and showed that their absence leads to lysosomal sphingosine accumulation which hints at a sphingosine transport role of both proteins. Furthermore, artificial elevation of lysosomal sphingosine levels impaired cholesterol efflux, consistent with sphingosine and cholesterol sharing a common export mechanism.
DOI:doi:10.1073/pnas.2213886120
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1073/pnas.2213886120
 DOI: https://doi.org/10.1073/pnas.2213886120
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Carrier Proteins
 Cholesterol
 Intracellular Signaling Peptides and Proteins
 lysosomal storage diseases
 Lysosomes
 Membrane Glycoproteins
 Membrane Transport Proteins
 Niemann-Pick C1 Protein
 organelle-targeted probes
 photocrosslinking
 protein-lipid interaction
 sphingolipids
 Sphingosine
 Sterols
K10plus-PPN:1896618723
Verknüpfungen:→ Zeitschrift

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