TY - JOUR
T1 - Trifunctional Sphinganine
T2 - A New Tool to Dissect Sphingolipid Function
AU - Farley, Scotland
AU - Stein, Frank
AU - Haberkant, Per
AU - Tafesse, Fikadu G.
AU - Schultz, Carsten
N1 - Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society.
PY - 2024/2/16
Y1 - 2024/2/16
N2 - Functions and cell biology of the sphingolipids sphingosine and sphinganine in cells are not well understood. While some signaling roles for sphingosine have been elucidated, the closely related sphinganine has been described only insofar as it does not elicit many of the same signaling responses. Here, we prepared multifunctionalized derivatives of the two lipid species that differ only in a single double bond of the carbon backbone. Using these novel probes, we were able to define their spatiotemporal distributions within cells. Furthermore, we used these tools to systematically map the protein interactomes of both lipids. The lipid-protein conjugates, prepared through photo-crosslinking in live cells and extraction via click chemistry to azide beads, revealed significant differences in the captured proteins, highlighting their distinct roles in various cellular processes. This work elucidates mechanistic differences between these critical lipids and sets the foundation for further studies of the cellular functions of sphingosine and sphinganine.
AB - Functions and cell biology of the sphingolipids sphingosine and sphinganine in cells are not well understood. While some signaling roles for sphingosine have been elucidated, the closely related sphinganine has been described only insofar as it does not elicit many of the same signaling responses. Here, we prepared multifunctionalized derivatives of the two lipid species that differ only in a single double bond of the carbon backbone. Using these novel probes, we were able to define their spatiotemporal distributions within cells. Furthermore, we used these tools to systematically map the protein interactomes of both lipids. The lipid-protein conjugates, prepared through photo-crosslinking in live cells and extraction via click chemistry to azide beads, revealed significant differences in the captured proteins, highlighting their distinct roles in various cellular processes. This work elucidates mechanistic differences between these critical lipids and sets the foundation for further studies of the cellular functions of sphingosine and sphinganine.
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U2 - 10.1021/acschembio.3c00554
DO - 10.1021/acschembio.3c00554
M3 - Article
C2 - 38284972
AN - SCOPUS:85184821241
SN - 1554-8929
VL - 19
SP - 336
EP - 347
JO - ACS chemical biology
JF - ACS chemical biology
IS - 2
ER -