The 3-hydroxy group and 4,5-trans double bond of sphingomyelin are essential for modulation of galactosylceramide transmembrane asymmetry

Barbara Malewicz, Jacob T. Valiyaveettil, Kochurani Jacob, Hoe Sup Byun, Peter Mattjus, Wolfgang J. Baumann, Robert Bittman, Rhoderick E Brown

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

The structural features of SPM that control the transbilayer distribution of β-GalCer in POPC vesicles were investigated by 13C- and 31P-NMR spectroscopy using lipid analogs that share physical similarities with GalCer or SPM. The SPM analogs included N-palmitoyl-4,5- dihydro-SPM, 3-deoxy-SPM, 1-alkyl-2-amidophosphatidylcholine, and dipalmitoylphosphatidylcholine, a popular model "raft lipid". The transbilayer distributions of the SPM analogs and SPM in POPC vesicles were similar by 31P-NMR. To observe the dramatic change in GalCer transbilayer distribution that occurs when SPM is included in POPC vesicles, the 3-OH group, 4,5-trans double bond, and amide linkage all were required in SPM. However, inclusion of 2 and 10 mol % dihydroSPM in SPM/POPC (1:1) vesicles mitigated and completely abrogated the effect of SPM on the transbilayer distribution of GalCer. Despite sharing some structural features with GalCer and localizing preferentially to the inner leaflet of POPC vesicles, dimyristoylphosphatidylethanolamine did not undergo a change in transbilayer distribution when SPM was incorporated into the vesicles. The results support the hypothesis that specific interactions may be favored among select sphingolipids in curvature-stressed membranes and emphasize the potential importance of the SPM-dihydroSPM ratio in membrane fission and fusion processes associated with vesicle biogenesis and trafficking.

Original languageEnglish (US)
Pages (from-to)2670-2680
Number of pages11
JournalBiophysical journal
Volume88
Issue number4
DOIs
StatePublished - Apr 2005

Bibliographical note

Funding Information:
We are grateful for support provided by the National Institute of General Medical Sciences-45928 (R.E.B.), the National Heart, Lung, and Blood Institute-16660 (R.B.), the National Institutes of Health RR-04654 (W.J.B.), The Academy of Finland (P.M.), and The Hormel Foundation.

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