Lipid Biology Laboratory

Our accumulating knowledge in lipid biology in these decades revealed that lipids are not simple bricks to build a membrane, rather, each lipid has a distinct function. However, our understanding on the role of lipids is still limited. The function of most of the membrane lipids seems to be dependent not only on the characteristic of individual lipid but on the dynamic equilibrium of the assembly of specific lipids. We are trying to address this question by "imaging" and "isolating" lipids and lipid domains. In "imaging lipids" project, we screen novel probes that recognize specific lipids and examine the dynamics of these lipids in living cells using the probes. "Isolating lipids" project is conducted to biochemically and biophysically analyze lipid domains after isolation from cells. We also reconstitute lipid domains from biochemically identified components. We hope our multidisciplinary approach leads to the elucidation of the multiple function of lipids and eventually to the establishment of a novel technique to manipulate lipid function.

Research Subjects

• Intracellular and intercellular lipid traffic
• Molecular mechanisms of organization and assembly of lipid membranes
• Lipid-protein interaction

Publications

1. Abe M, Makino A, Hullin-Matsuda F, Kamijo K, Ohno-Iwashita Y, Hanada K, Mizuno H, Miyawaki A, and Kobayashi T:
   "A role for sphingomyelin-rich lipid domains in the accumulation of PIP2 to the cleavage furrow during cytokinesis."
   Mol. Cell. Biol. 32,1396-1407 (2012)
2. Tan H-H, Makino A, Sudesh K, Greimel P, and Kobayashi T:
   "Spectroscopic evidence for the unusual stereochemical configuration of an endosome-specific lipid."
   Angew. Chem. Int. Ed. Engl. 51, 533-535 (2012)
3. Hullin-Matsuda F, Tomishige N, Sakai S, Ishitsuka R, Ishii K, Makino A, Greimel P, Abe M, Laviad EL, Lagarde M, Vidal H, Saito T, Osada H, Hanada K, Futerman AH, Kobayashi T.:
   "Limonoid compounds inhibit sphingomyelin biosynthesis by preventing CERT protein-dependent extraction of ceramides from the endoplasmic reticulum."
   J Biol Chem 287, 24397-24411 (2012)
4. Takahashi, M., Murate, M., Fukuda, M., Sato, S. B., Ohta, A., and Kobayashi, T.:
   "Cholesterol controls lipid endocytosis through rab11"
   Mol. Biol. Cell 18, 2667-2677 (2007)
5. Hayakawa, T., Makino, A., Murate, M., Sugimoto, I., Hashimoto, Y., Takahashi, H., Ito, K., Fujisawa, T., Matsuo, H., and Kobayashi, T.:
   "pH-dependent formation of membranous cytoplasmic body-like structure of ganglioside GM1/bis(monoacylglycero)phosphate mixed membranes"
   Biophys. J. 92, L13-16 (2007)
6. Kiyokawa, E., Baba, T., Otsuka, N., Makino, A., Ohno, S., and Kobayashi, T.:
   "Spatial and functional heterogeneity of sphingolipid-rich membrane domains"
   J. Biol. Chem., 280, 24072-24084, (2005)
7. Ishitsuka, R., Yamaji-Hasegawa, A., Makino, A., Hirabayashi, Y., and Kobayashi, T.:
   "A Lipid-specific toxin reveals heterogeneity of sphingomyelin-containing membranes"
   Biophys. J., 86, 296-307 (2004)
8. Sato, S.B., Ishii, K., Makino, A., Iwabuchi, K., Yamaji-Hasegawa, A., Senoh, Y., Nagaoka, I., Sakuraba, H., and Kobayashi, T.:
   "Distribution and transport of cholesterol-rich membrane domains monitored by a membrane-impermeant fluorescent polyethylene glycol-derivatized cholesterol"
   J. Biol. Chem., 279, 23790-23796 (2004)
9. Yamaji-Hasegawa, A., Makino, A., Baba, T., Senoh, Y., Kimura-Suda, H., Sato, SB., Terada, N., Ohno, S., Kiyokawa, E., Umeda, M., and Kobayashi, T.:
   "Oligomerization and pore formation of a sphingomyelin-specific toxin, lysenin"
   J. Biol. Chem 278, 22762-22770 (2003)
10. Makino, A., Baba, T., Fujimoto, K., Iwamoto, K., Yano, Y., Terada, N., Ohno, S., Sato, SB., Ohta, A., Umeda, M., Matsuzaki, K., and Kobayashi, T.:
    "Cinnamycin (Ro09-0198) promotes cell binding and toxicity by inducing transbilayer lipid movement"
    J. Biol. Chem, 278, 3204-3209 (2003)