PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
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)
Publ. Version/Full Text DOI PMC
Open Access Hybrid
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
9.412
2.539
11
16
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Signaling Lipids ; Diacylglycerol ; Protein Kinase C ; Mathematical Modeling ; Caged Lipid Probes; Kinase-c; Cholesterol; Metabolism; Activation; Channels; Ca2+
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 117, Issue: 14, Pages: 7729-7738 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Publishing Place 2101 Constitution Ave Nw, Washington, Dc 20418 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502600-002
DOI 10.1073/pnas.1912684117
WOS ID WOS:000524486300032
Scopus ID 85083107154
PubMed ID 32213584
Erfassungsdatum 2020-04-02
[➜Report correction]