Bifunctional sphingosine for cell-based analysis of protein-sphingolipid interactions

• Verfasst von: Haberkant, Per [VerfasserIn]
• Verfasst von: Stein, Frank [VerfasserIn]
• Verfasst von: Höglinger, Doris [VerfasserIn]
• Verfasst von: Gerl, Mathias [VerfasserIn]
• Verfasst von: Brügger, Britta [VerfasserIn]
• Verfasst von: Van Veldhoven, Paul P. [VerfasserIn]
• Verfasst von: Krijgsveld, Jeroen [VerfasserIn]
• Verfasst von: Gavin, Anne-Claude [VerfasserIn]
• Verfasst von: Schultz, Carsten [VerfasserIn]
• Titel: Bifunctional sphingosine for cell-based analysis of protein-sphingolipid interactions
• Verf.angabe: Per Haberkant, Frank Stein, Doris Höglinger, Mathias J. Gerl, Britta Brügger, Paul P. Van Veldhoven, Jeroen Krijgsveld, Anne-Claude Gavin, and Carsten Schultz
• Jahr: 2016
• Jahr des Originals: 2015
• Umfang: 9 S.
• Fussnoten: Published: November 11, 2015 ; Gesehen am 02.09.2020
• Titel Quelle: Enthalten in: American Chemical SocietyACS chemical biology
• Ort Quelle: Washington, DC : Soc., 2006
• Jahr Quelle: 2016
• Band/Heft Quelle: 11(2016), 1, Seite 222-230
• ISSN Quelle: 1554-8937
• DOI: doi:10.1021/acschembio.5b00810
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1728591244

Abstract

Sphingolipids are essential structural components of cellular membranes and are crucial regulators of cellular processes. While current high-throughput approaches allow for the systematic mapping of interactions of soluble proteins with their lipid-binding partners, photo-cross-linking is the only technique that enables for the proteome-wide mapping of integral membrane proteins with their direct lipid environment. Here, we report the synthesis of a photoactivatable and clickable analog of sphingosine (pacSph). When administered to sphingosine-1-phosphate lyase deficient cells, pacSph allows its metabolic fate and the subcellular flux of de novo synthesized sphingolipids to be followed in a time-resolved manner. The chemoproteomic profiling yielded over 180 novel sphingolipid-binding proteins, of which we validated a number, demonstrating the unique value of this technique as a discovery tool. This work provides an important resource for the understanding of the global cellular interplay between sphingolipids and their interacting proteins.