Department of Biochemistry and Molecular Biology

Biological Science

Role of tight junctions in higher-order biological functions
  • Exploring novel molecules essential to tight junctions
  • Exploring barrier construction at the molecular to whole-animal level
  • Claudin structure, function, and manipulation of barrier function
  • Function and structure of the tight junction-apical complex
  • Imaging of the tight junction and intracellular structure
Professor TSUKITA Sachiko
Biological Science
Beginning with Professor Tadamitsu Kishimoto, the lab has existed under the leadership of Professors Michihiko Tada and Iichiro Shimomura

To see, to think, and to do science," from the viewpoint, "from molecules toward biological systems

Epithelial cell sheets are formed by epithelial cells that adhere tightly to each other via tight junctions (TJs). In addition to partitioning different compartments in the body, these sheets have primary roles in morphogenesis and in creating microenvironments that support higher biological functions. Our laboratory specializes in TJ research, from the level of molecules to biological systems.

Our lab developed methods for isolating TJs and their associated structures [1], which led to the discovery of a number of molecules essential to TJs, including claudin, occludin, tricellulin, and ZO1 [2,3]. This work also elucidated the critical role of the apical side of the epithelial cell sheets, the surface of many biological systems. In this context, the discovery of Odf2, a member of the ERM family [4-7], has expanded our research.

In addition, we are conducting mouse-level experiments on TJ proteins, such as claudins, using KO mice and cultured cells. These studies have revealed the barrier function of claudin, as well as its sometimes very specific permeability for ions and solutes [8, 9]. Other studies from the lab have clarified the claudin structure [10, 11]. This information has increased our understanding of TJ structure and function, of the barrier functions it regulates, and of new therapies related to this system.

Finally, we are investigating the “TJ-apical complex,” a system composed of the TJ, the apical membrane, and the associated cytoskeleton-TJ complexes. We have discovered a new cytoskeletal network that is associated with TJs, and is complexed with other associated skeletal structures [6, 11, 12]. These complexes have been confirmed in various systems, such as multiciliated cells, and we are investigating their function and structure [13]. Part of this research involves the development of a live-imaging system that can observe living tissue for a long time with high resolution, to reveal the dynamic properties of these TJ complexes. This information will increase our understanding of intercellular barriers.

【References】

1.Tsukita S, Tsukita S. J.Cell Biol. 108(1):31-41, 1989.
2.Ikenouchi et al. J.Cell Biol. 171:939-45, 2005.
3.Umeda et al. Cell 26:741-54, 2006.
4.Tsukita at al. J.Cell Biol.126(2):391-401, 1994.
5.Ishikawa et al. Nat.Cell Biol. 7(5):517-24, 2005.
6.Kunimoto et al. Cell 148(1-2):189-200, 2012.
7. Nojima et al. Nat Cell Biol. 10(8):971-8, 2008
8.Hayashi et al. Gastroenterology 142(2):292-304, 2012.
9.Matsumoto et al. Gastroenterology 147(5):1134-45, 2014.
10.Suzuki et al. Science 344(6181):304-7, 2014.
11.Saitoh et al. Science 347(6223):775-8, 2015.
12.Yano et al. J.Cell Biol. 203(4):605-14, 2013.
13.Tateishi et al. Sci. Rep. 7:43783, 2017
14.Herawati et al. J.Cell Biol. 214(5):571-86, 2016.