This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ishitsuka, R. Articles by Kobayashi, T. Search for Related Content PubMed PubMed Citation Articles by Ishitsuka, R. Articles by Kobayashi, T.

A Lipid-Specific Toxin Reveals Heterogeneity of Sphingomyelin-Containing Membranes

Reiko Ishitsuka ^*, Akiko Yamaji-Hasegawa ^*, Asami Makino ^*, Yoshio Hirabayashi  and Toshihide Kobayashi ^* 

^* Supra-Biomolecular System Research Group, RIKEN (Institute of Physical and Chemical Research) Frontier Research System, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan; Neuronal Circuit Mechanisms Research Group, Brain Science Institute, RIKEN, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan; and INSERM U585, Institut Multidisciplinaire de Biochimie des Lipides (IMBL), Institut National des Sciences Appliquees, Lyon, 69621 Villeurbanne, France

Correspondence: Address reprint requests to Toshihide Kobayashi, Supra-Biomolecular System Research Group, RIKEN (Institute of Physical and Chemical Research) Frontier Research System, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan. Tel.: +81-48-467-9612; Fax: +81-48-467-8693; E-mail: kobayasi{at}postman.riken.go.jp.

Little is known about the heterogenous organization of lipids in biological membranes. Sphingomyelin (SM) is a major plasma membrane lipid that forms lipid domains together with cholesterol and glycolipids. Using SM-specific toxin, lysenin, we showed that in cultured epithelial cells the accessibility of the toxin to SM is different between apical and basolateral membranes. Apical membranes are highly enriched with glycolipids. The inhibitory role of glycolipids in the binding of lysenin to SM was confirmed by comparing the glycolipid-deficient mutant melanoma cell line with its parent cell. Model membrane experiments indicated that glycolipid altered the local density of SM so that the affinity of the lipid for lysenin was decreased. Our results indicate that lysenin recognizes the heterogenous organization of SM in biomembranes and that the organization of SM differs between different cell types and between different membrane domains within the same cell. Isothermal titration calorimetry suggests that lysenin binding to SM is presumably the result of a SM-lysenin complex formation of specific stoichiometry, thus supporting the idea of the existence of small condensed lipid complexes consisting of just a few lipid molecules in living cells.

This article has been cited by other articles:

				T. K. Hailemariam, C. Huan, J. Liu, Z. Li, C. Roman, M. Kalbfeisch, H. H. Bui, D. A. Peake, M.-S. Kuo, G. Cao, et al. Sphingomyelin Synthase 2 Deficiency Attenuates NF{kappa}B Activation Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1519 - 1526. [Abstract] [Full Text] [PDF]

				T. Ding, Z. Li, T. Hailemariam, S. Mukherjee, F. R. Maxfield, M.-P. Wu, and X.-C. Jiang SMS overexpression and knockdown: impact on cellular sphingomyelin and diacylglycerol metabolism, and cell apoptosis J. Lipid Res., February 1, 2008; 49(2): 376 - 385. [Abstract] [Full Text] [PDF]

				K. Iwamoto, T. Hayakawa, M. Murate, A. Makino, K. Ito, T. Fujisawa, and T. Kobayashi Curvature-Dependent Recognition of Ethanolamine Phospholipids by Duramycin and Cinnamycin Biophys. J., September 1, 2007; 93(5): 1608 - 1619. [Abstract] [Full Text] [PDF]

				R. D. Singh, Y. Liu, C. L. Wheatley, E. L. Holicky, A. Makino, D. L. Marks, T. Kobayashi, G. Subramaniam, R. Bittman, and R. E. Pagano Caveolar Endocytosis and Microdomain Association of a Glycosphingolipid Analog Is Dependent on Its Sphingosine Stereochemistry J. Biol. Chem., October 13, 2006; 281(41): 30660 - 30668. [Abstract] [Full Text] [PDF]

				Y. Nagata, H. Kobayashi, M. Umeda, N. Ohta, S. Kawashima, P. S. Zammit, and R. Matsuda Sphingomyelin Levels in the Plasma Membrane Correlate with the Activation State of Muscle Satellite Cells J. Histochem. Cytochem., April 1, 2006; 54(4): 375 - 384. [Abstract] [Full Text] [PDF]

				J. E. Shaw, R. F. Epand, R. M. Epand, Z. Li, R. Bittman, and C. M. Yip Correlated Fluorescence-Atomic Force Microscopy of Membrane Domains: Structure of Fluorescence Probes Determines Lipid Localization Biophys. J., March 15, 2006; 90(6): 2170 - 2178. [Abstract] [Full Text] [PDF]

				E. Kiyokawa, T. Baba, N. Otsuka, A. Makino, S. Ohno, and T. Kobayashi Spatial and Functional Heterogeneity of Sphingolipid-rich Membrane Domains J. Biol. Chem., June 24, 2005; 280(25): 24072 - 24084. [Abstract] [Full Text] [PDF]

				R. Ishitsuka, S. B. Sato, and T. Kobayashi Imaging Lipid Rafts J. Biochem., March 1, 2005; 137(3): 249 - 254. [Abstract] [Full Text] [PDF]