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Schuhmacher, M.* ; Grasskamp, A.T.* ; Barahtjan, P.* ; Wagner, N.* ; Lombardot, B.* ; Schuhmacher, J.S.* ; Sala, P. ; Lohmann, A.* ; Henry, I.* ; Shevchenko, A.* ; Coskun, Ü. ; Walter, A.M.* ; Nadler, A.*

Live-cell lipid biochemistry reveals a role of diacylglycerol side-chain composition for cellular lipid dynamics and protein affinities.

Proc. Natl. Acad. Sci. U.S.A. 117, 7729-7738 (2020)
Verlagsversion DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Every cell produces thousands of distinct lipid species, but insight into how lipid chemical diversity contributes to biological signaling is lacking, particularly because of a scarcity of methods for quantitatively studying lipid function in living cells. Using the example of diacylglycerols, prominent second messengers, we here investigate whether lipid chemical diversity can provide a basis for cellular signal specification. We generated photo-caged lipid probes, which allow acute manipulation of distinct diacylglycerol species in the plasma membrane. Combining uncaging experiments with mathematical modeling, we were able to determine binding constants for diacylglycerol-protein interactions, and kinetic parameters for diacylglycerol transbilayer movement and turnover in quantitative live-cell experiments. Strikingly, we find that affinities and kinetics vary by orders of magnitude due to diacylglycerol side-chain composition. These differences are sufficient to explain differential recruitment of diacylglycerol binding proteins and, thus, differing downstream phosphorylation patterns. Our approach represents a generally applicable method for elucidating the biological function of single lipid species on subcellular scales in quantitative live-cell experiments.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Signaling Lipids ; Diacylglycerol ; Protein Kinase C ; Mathematical Modeling ; Caged Lipid Probes; Kinase-c; Cholesterol; Metabolism; Activation; Channels; Ca2+
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Quellenangaben Band: 117, Heft: 14, Seiten: 7729-7738 Artikelnummer: , Supplement: ,
Verlag National Academy of Sciences
Verlagsort 2101 Constitution Ave Nw, Washington, Dc 20418 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)