Laboratories

Molecular Medicine and Cell Biology

Outline of Research and Education

The cellular membrane is the essential component of cells that distinguishes the inside and the outside of the cells. The membrane receives every stimulus to cells, but how it behaves is not well understood. Our lab focuses on the membrane-binding proteins connecting the membrane to the intracellular signaling for varieties of cellular functions including proliferation and morphological changes. The roles of lipid composition of the membrane, including the saturation or unsaturation of fatty acids, are examined using the membrane-binding proteins.

Major Research Topics

Elucidating cell-shape dependent intracellular signaling

The intracellular signaling cascade became understood by observing molecule-molecule interactions. However, the spatial organization of these signaling cascades had not been studied so well. We found the BAR domain superfamily proteins that remodel membrane shape and then, presumably, dictate the intracellular signaling cascades. Thus, the important questions are how the BAR domain superfamily proteins are regulated, and how they assemble the downstream molecules.

Searching for new membrane binding proteins

Given the importance of membrane lipids as essential components of cells, we suppose there are many lipid-binding molecules that have not been clarified. We are searching for novel lipid-binding proteins using a variety of methods.

The importance of fatty acids in the membrane.

Another point for understanding the cellular membrane is the importance of fatty-acid tails of lipids. Although the importance of saturated or unsaturated lipids in nutrients is well-known, the mechanism of importance is not understood in molecular levels in cell biology. We will examine how fatty acids are important in intracellular signaling including that for cancer, using the proteins listed above.

References

  1. Senju, Y. et al., J Cell Sci, 10, 1242/jcs.167775, 2015
  2. Takahashi, N.et al., Nat Commun, 5.10.1038/ncomms5994 , 2014
  3. Suetsugu, S. et al., Physiological reviews, 94, 1219-1248, 2014
  4. Suetsugu, S., Seminars in cell &anmp; developmental biology, 24, 267-271, 2013
  5. Oikawa, T., et al., PloS One, 8, e60528, 2013
  6. Suetsugu, S., Seminars in Cell & Developmental Biology, 24, 267-271, 2013
  7. Suetsugu, S. and Itoh, Y., seikagaku, 84, 30-35, 2012
  8. Suetsugu, S. and Gautreau, A., Trends in Cell Biology, 22, 141-150, 2012
  9. Senju, Y., et al., Journal of Cell Science, 124, 2032-2040, 2011
  10. Shimada, A., et al., FEBS letters, 584, 1111-1118, 2010
  11. Takano, K., et al., Science, 330, 1536-1540, 2010
  12. Takano, K., et al. EMBO journal 27, 2817-2828, 2008
  13. Scita, G., et al. Trends in Cell Biology 18, 52-60, 2008
  14. Shimada, A., et al. Cell 129, 761-772, 2007
  15. Takenawa, T. and Suetsugu, S. Nature Reviews. Molecular Cell Biology 8, 37-48, 2007
  16. Suetsugu, S., et al. Journal of Biological Chemistry 281, 35347-35358, 2006
  17. Suetsugu, S., et al. Journal of Cell Biology 173, 571-585, 2006
Fig.1
Fig. 1 Location of BAR domain functions in cells. The BAR domains function as polymers at submicron-scale invaginations, such as clathrin-coated pits and caveolae, as well as in protrusions, including filopodia and lamellipodia. The typical scales for clathrin-coated pits and caveolae are 100-200 nm and 50-100 nm in diameter, respectively. The BAR domains have typically been approximated as arcs of 20-25 nm in length with a diameter of 3-6 nm. The membrane thickness is typically approximately 5 nm.
Fig.2
Fig. 2 Wire-frame model of the clathrin-coated pit. The BAR proteins are shown in yellow, and the actin cytoskeleton is shown in magenta. The membrane is in wire-frame. The actin filaments are thought to be finely organized on the nano-scale membrane invaginations of the clathrin coated pits.
Fig.3
Fig. 3 Schematic diagram of the cellular membrane. Each lipid molecule consists of one hydrophilic head and two hydrophobic fatty-acid tails. There are varieties of combination of head, such as serine, ethanolamine, and so on, and various saturated and unsaturated fatty acids, such as palmitic acid (saturated), oleic acid (monounsaturated), etc.
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