HOME > Members > GCOE Organizing Members > Toyoshi Fujimoto MD, PhD

Toyoshi Fujimoto MD, PhDProfessor, Department of Molecular Cell Biology, Nagoya University Graduate School of Medicine


Specialized field

Anatomy and Cell Biology

Career Summary

March, 1978
Graduated from Kyoto University Faculty of Medicine
April, 1978
Assistant Professor, Department of Anatomy Kyoto University Faculty of Medicine
February, 1982
Associate Professor, Department of Anatomy
Kyoto University Faculty of Medicine
May, 1995
Professor and Chairman
Department of Anatomy and Cell Biology
Gunma University School of Medicine
April, 1999-present
Professor and Chairman
Department of Anatomy and Molecular Cell Biology
Nagoya University Graduate School of Medicine

Research Theme

Nano-scale analysis of lipid-based structures

Research Summary

Research Purpose and Results:

[1] We previously reported that apolipoprotein B100 (ApoB) is deposited around lipid droplets (LDs) and forms a structure that we called as the "ApoB-crescent". In the present project, we obtained the following results: 1) ApoB in the ApoB-crescent is lipidated by the MTP activity; 2) the ApoB-crescent is made of a thin ER-related cistern and an LD fusing to it; 3) lipidated ApoB accumulates in the lumen of the thin ER-related cistern; 4) the limiting membrane of the ER-related cistern is enriched with free cholesterol. The result showed that lipid esters can accumulate between the two phospholipid layers of the biomembrane and suggested a close functional linkage between the LD formation and the lipoprotein synthesis.

[2] By developing a method to analyze membrane lipids at the nanoscale, we revealed that PI(4,5)P2 accumulates at the orifice of caveolae and coated pits. Upon agonist stimulation, PI(4,5)P2 in caveolae and coated pits showed distinct behaviors from that in the flat undifferentiated membrane. The result verified the presence of different PI(4,5)P2 pools in the cell membrane for the first time.

Principal Research Achievement

  1. Fujita A, Fujimoto, T. Nanoscale Analysis of Glycolipid Distribution in the Cell Membrane. Trends Glycosci Glycotech, in press (2010)
  2. Fujita A, Cheng J, Fujimoto T. Quantitative electron microscopy for the nanoscale analysis of membrane lipid distribution. Nature Protocols, 5, 661-669 (2010)
  3. Ohsaki S, Shinohara Y, Suzuki M, Fujimoto T, A pitfall in using BODIPY dyes for lipid droplet labeling. Histochem Cell Biol, 133, 477-480 (2010)
  4. Fujita A, Fujimoto T. High Resolution Molecular Localization by Freeze-Fracture Replica Labeling, Schwartzbach SD, Osafune T (eds.), Immuno-electron Microscopy. Methods Mol Biol, 657, 205-216 (2010)
  5. Fujita A, Cheng J, Tauchi-Sato K, Takenawa T, Fujimoto T. A distinct pool of phosphatidyl- inositol 4,5-bisphosphate in caveolae revealed by a nanoscale labeling technique. Proc Natl Acad Sci USA, 106, 9256-9261 (2009)
  6. Fujita A, Cheng J, Fujimoto T. Segregation of GM1 and GM3 clusters in the cell membrane depends on the intact actin cytoskeleton. Biochim Biophys Acta, 1791, 388-396 (2009)
  7. Cheng J, Fujita A, Ohsaki Y, Suzuki M, Shinohara Y, Fujimoto T. Quantitative electron microscopy shows uniform incorporation of triglycerides into existing lipid droplets. Histochem Cell Biol, 132, 281-291 (2009)
  8. Ohsaki Y, Cheng J, Suzuki M, Shinohara Y, Fujita A, Fujimoto T. Biogenesis of cytoplasmic lipid droplets: from the lipid ester globule in the membrane to the visible structure. Biochim Biophys Acta, 1791, 399-407 (2009)
  9. Ohsaki Y, Cheng J, Suzuki M, Fujita A, Fujimoto T. Lipid droplets are arrested in the ER membrane by tight binding of lipidated apolipoprotein B-100. J Cell Sci, 121, 2415-2422 (2008)
  10. Nishino N, Tamori Y, Tateya S, Kawaguchi T, Shibakusa T, Mizunoya W, Inoue K, Kitazawa R, Kitazawa S, Matsuki Y, Hiramatsu R, Masubuchi S, Omachi A, Kimura K, Saito M, Amo T, Ohta S, Yamaguchi T, Osumi T, Cheng J, Fujimoto T, Nakao H, Nakao K, Aiba A, Okamura H, Fushiki T, Kasuga M. FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets. J Clin Invest, 118, 2808-2821 (2008)
  11. Urahama Y, Ohsaki Y, Fujita Y, Maruyama S, Yuzawa Y, Matsuo S, Fujimoto T. Lipid droplet-associated proteins protect renal tubular cells from fatty acid-induced apoptosis. Am J Pathol, 173, 1286-1294 (2008)
  12. Kurahashi M, Niwa Y, Cheng J, Ohsaki Y, Fujita A, Goto, H, Fujimoto T, Torihashi S. Platelet-derived growth factor signals play critical roles in differentiation of longitudinal smooth muscle cells in mouse embryonic gut. Neurogastroenterol Motil, 20, 521-531 (2008)
  13. Fujimoto T, Ohsaki Y, Cheng J, Suzuki M, Shinohara Y. Lipid droplets: a classic organelle with a new outfit. Histochem Cell Biol, 136, 263-279 (2008)
  14. Fujita A et al. Gangliosides GM1 and GM3 in the living cell membrane form clusters susceptible to cholesterol depletion and chilling. Mol. Biol. Cell 18: 2812-2822 (2007)
  15. Ohsaki Y et al. Cytoplasmic lipid droplets are sites of convergence of proteasomal and autophagic degradation of apolipoprotein B. Mol. Biol. Cell 17: 2674-2683 (2006)
  16. Ozeki S et al. Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane. J. Cell Sci. 118: 2601-2611 (2005)
  17. Nomura R et al. Human coronavirus 229E binds to CD13 in raft and enters the cell through caveolae. J. Virol. 78: 8701-8708 (2004)
  18. Kogo H et al. Cell type-specific occurrence of caveolin-1alpha and -1beta in the lung caused by expression of distinct mRNAs. J. Biol. Chem. 279: 25574-25581 (2004)
  19. Tauchi-Sato K et al. The surface of lipid droplets is a phospholipid monolayer with a unique fatty acid composition. J. Biol. Chem. 277: 44507-44512 (2002)
  20. Torihashi S et al. Calcium oscillation linked to pacemaking of interstitial cell of Cajal; requirement of calcium influx and localisation of TRP4 in caveolae. J. Biol. Chem. 277: 19191-19197 (2002)
  21. Fujimoto T et al. Caveolin-2 is targeted to lipid droplets, a new ‘membrane domain’ in the cell. J. Cell Biol. 152: 1079-1085 (2001)
  22. Fujimoto T et al. Isoforms of caveolin-1 and caveolar structure. J. Cell Sci. 113: 3509-3517 (2000)
  23. Nomura R et al. Tyrosine phosphorylated caveolin-1: immunolocalization and molecular characterization. Mol. Biol. Cell 10: 975-986 (1999)
  24. Isshiki M et al. Endothelial Ca2+ waves preferentially originate at specific loci in caveolin-rich cell edges. Proc. Natl. Acad. Sci. USA. 95: 5009-5014 (1998)
  25. Saitou M et al. Occludin-deficient embryonic stem cells can differentiate into polarized epithelial cells bearing well-developed tight junctions. J. Cell Biol. 141: 397-408 (1998)
  26. Yamamoto-Hino M et al. Apical vesicles bearing inositol 1,4,5-trisphosphate receptors in the Ca2+ initiation site of ductal epithelium of submandibular gland. J. Cell Biol. 141: 135-142 (1998)
  27. Fujimoto K et al. Transmembrane phospholipid distribution revealed by freeze-fracture replica labeling. J. Cell Sci. 109: 2453-2460 (1996)
  28. Fujimoto T et al. Inositol 1,4,5-trisphosphate receptor-like protein in plasmalemmal caveolae is linked to actin filaments. J. Cell Sci. 108: 7-15 (1995)
  29. Fujimoto T. Calcium pump of the plasma membrane is localized in caveolae. J. Cell Biol. 120: 1147-1157 (1993)
  30. Fujimoto T et al. Localization of inositol 1,4,5-trisphosphate receptor-like protein in plasmalemmal caveolae. J. Cell Biol. 119: 1507-1513 (1992)
  31. Fujimoto T et al. Fodrin in the human polymorphonuclear leucocyte: redistribution induced by the chemotactic peptide. J. Cell Sci. 96: 477-484 (1990)
  32. Fujimoto T et al. Immunocytochemical studies of endothelial cells in vivo. I. The presence of desmin only, or of desmin plus vimentin, or vimentin only, in the endothelial cells of different capillaries of the adult chicken. J. Cell Biol. 103: 2775-2786 (1986)

Award

1988 Young Investigator Award
(The 8th International Congress on Histochemistry and Cytochemistry)
1996 Seto Award (The Society Award of The Japanese Society for Electron Microscopy)

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