Abstract:
:Lipid composition affects the biophysical properties of membranes that provide a platform for receptor-mediated cellular signaling. To study the regulatory role of membrane lipid composition, we combined genetic perturbations of sphingolipid metabolism with the quantification of diverse steps in Toll-like receptor (TLR) signaling and mass spectrometry-based lipidomics. Membrane lipid composition was broadly affected by these perturbations, revealing a circular network of coregulated sphingolipids and glycerophospholipids. This evolutionarily conserved network architecture simultaneously reflected membrane lipid metabolism, subcellular localization, and adaptation mechanisms. Integration of the diverse TLR-induced inflammatory phenotypes with changes in lipid abundance assigned distinct functional roles to individual lipid species organized across the network. This functional annotation accurately predicted the inflammatory response of cells derived from patients suffering from lipid storage disorders, based solely on their altered membrane lipid composition. The analytical strategy described here empowers the understanding of higher-level organization of membrane lipid function in diverse biological systems.
journal_name
Celljournal_title
Cellauthors
Köberlin MS,Snijder B,Heinz LX,Baumann CL,Fauster A,Vladimer GI,Gavin AC,Superti-Furga Gdoi
10.1016/j.cell.2015.05.051subject
Has Abstractpub_date
2015-07-02 00:00:00pages
170-83issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(15)00641-8journal_volume
162pub_type
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