title: Changes in membrane biophysical properties induced by sphingomyelinase depend on the sphingolipid N-acyl chain.
abstract: Ceramide (Cer) is involved in the regulation of several cellular processes by mechanisms that depend on Cer-induced changes on membrane biophysical properties. Accumulating evidence shows that Cers with different N-acyl chain composition differentially impact cell physiology, which may in part be due to specific alterations in membrane biophysical properties. We now address how the sphingolipid (SL) N-acyl chain affects membrane properties in cultured human embryonic kidney cells by overexpressing different Cer synthases (CerSs). Our results show an increase in the order of cellular membranes in CerS2-transfected cells caused by the enrichment in very long acyl chain SLs. Formation of Cer upon treatment of cells with bacterial sphingomyelinase promoted sequential changes in the properties of the membranes: after an initial increase in the order of the fluid plasma membrane, reorganization into domains with gel-like properties whose characteristics are dependent on the acyl chain structure of the Cer was observed. Moreover, the extent of alterations of membrane properties correlates with the amount of Cer formed. These data reinforce the significance of Cer-induced changes on membrane biophysical properties as a likely molecular mechanism by which different acyl chain Cers exert their specific biological actions.
authors.affiliation: Centro de Química-Física Molecular and Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal.
authors.forename: Sandra N
authors.initials: SN
authors.lastname: Pinto
authors.forename: Elad L
authors.initials: EL
authors.lastname: Laviad
authors.forename: Johnny
authors.initials: J
authors.lastname: Stiban
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Kelly
authors.forename: Alfred H
authors.initials: AH
authors.lastname: Merrill
authors.forename: Manuel
authors.initials: M
authors.lastname: Prieto
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Futerman
authors.forename: Liana C
authors.initials: LC
authors.lastname: Silva
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D002518:Ceramides / Q000096:biosynthesis*; D005454:Fluorescence Polarization; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D013107:Sphingolipids / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000502:physiology*; D051049:Sphingosine N-Acyltransferase / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D002518:Ceramides; D008565:Membrane Proteins; D013107:Sphingolipids; D025521:Tumor Suppressor Proteins; C438311:CERS2 protein, human; D051049:Sphingosine N-Acyltransferase; D013108:Sphingomyelin Phosphodiesterase
keywords: acyl chain structure; ceramide; ceramide synthases; lipid domains; membrane remodeling; sphingolipids