Ablation of ceramide synthase 2 strongly affects biophysical properties of membranes.
Little is known about the effects of altering sphingolipid (SL) acyl chain structure and composition on the biophysical properties of biological membranes. We explored the biophysical consequences of depleting very long acyl chain (VLC) SLs in membranes prepared from lipid fractions isolated from a ceramide synthase 2 (CerS2)-null mouse, which is unable to synthesize C22-C24 ceramides. We demonstrate that ablation of CerS2 has different effects on liver and brain, causing a significant alteration in the fluidity of the membrane and affecting the type and/or extent of the phases present in the membrane. These changes are a consequence of the depletion of VLC and unsaturated SLs, which occurs to a different extent in liver and brain. In addition, ablation of CerS2 causes changes in intrinsic membrane curvature, leading to strong morphological alterations that promote vesicle adhesion, membrane fusion, and tubule formation. Together, these results show that depletion of VLC-SLs strongly affects membrane biophysical properties, which may compromise cellular processes that critically depend on membrane structure, such as trafficking and sorting.
iMed.UL, Research Institute for Medicines and Pharmaceutical Sciences, Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisboa, Portugal; Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel; CQFM & IN, Instituto Superior Técnico, 1049-001 Lisboa, Portugal. Electronic address: lianacsilva@ff.ul.pt.
Liana C
LC
Silva
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Oshrit
O
Ben David
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Yael
Y
Pewzner-Jung
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Elad L
EL
Laviad
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Johnny
J
Stiban
School of Biology and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0230.
Sibali
S
Bandyopadhyay
School of Biology and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0230.
Alfred H
AH
Merrill
CQFM & IN, Instituto Superior Técnico, 1049-001 Lisboa, Portugal.
Manuel
M
Prieto
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Anthony H
AH
Futerman
D000818:Animals; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008861:Microsomes / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013107:Sphingolipids / Q000378:metabolism
D013107:Sphingolipids; D010088:Oxidoreductases; C108138:dihydroceramide desaturase