Bifunctional Sphingosine for Cell-Based Analysis of Protein-Sphingolipid Interactions

Per Haberkant, Frank Stein, Doris Höglinger, Mathias J. Gerl, Britta Brügger, Paul P. Van Veldhoven, Jeroen Krijgsveld, Anne Claude Gavin, Carsten Schultz

Research output: Contribution to journalArticle

50 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)222-230
Number of pages9
JournalACS Chemical Biology
Issue number1
StatePublished - Jan 15 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Medicine(all)

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  • Cite this

    Haberkant, P., Stein, F., Höglinger, D., Gerl, M. J., Brügger, B., Van Veldhoven, P. P., Krijgsveld, J., Gavin, A. C., & Schultz, C. (2016). Bifunctional Sphingosine for Cell-Based Analysis of Protein-Sphingolipid Interactions. ACS Chemical Biology, 11(1), 222-230.