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The Dawn of Barriology

Belt-like tight junctions (TJs), referred to as zonula occludens, have long been regarded as a specialized differentiation of epithelial cell membranes. They are required for cell adhesion and paracellular barrier functions. Recently, the molecular bases of TJs have gradually been unveiled. TJs are constructed by TJ strands, whose basic frameworks are composed of integral membrane proteins with four transmembrane domains, designated claudins. Recent functional analyses of claudins in cell cultures and in mice have suggested that claudin-based TJs may have pivotal functions in the regulation of the epithelial microenvironment, which is critical for various biological functions such as control of cell proliferation. These represent the dawn of ‘Barriology’ (defined by Shoichiro Tsukita as the science of barriers in multicellular organisms). TJs are the gatekeepers of blood-tissue barriers and as such play a crucial role in maintaining the integrity of the body.

Shoichiro Tsukita, one of the pioneers and enablers of Barriology, was born July 7, 1953 in Kobe, Japan.   He earned both an M.D. and a Ph.D. at the University of Tokyo.  While studying at the university, he met Sachiko.  The two of them married and worked together in the lab.  Shoichiro Tsukita was a professor at the National Institute for Physiological Sciences at Kyoto University when he published his seminal discovery of claudin 1 and 2 (Furuse et al. J Cell Biol. 1998 Jun 29;141(7):1539-50).  He also lectured at the University of Tokyo and worked as the director of the Department of Ultrastructural Research in Tokyo.  After a struggle against pancreatic cancer, Dr. Shoichiro Tsukita died on December 11, 2005.

Dr. Tsukita made many contributions to the study of tight junctions.  He had a great understanding of cell structure due to his time studying histology and electron microscopy.  His work started with isolating the area of the cell that held the tight junction, adherens junction, and desmosome.  His lab isolated occludin first.  At first, they thought occludin was the most important protein at the junction; however, they discovered that occludin knock-out mice retained tight junction functions.  They began searching for another protein.  Using a sugar gradient, graduate student Mikio Furuse was able to isolate claudins, the main components of tight junctions, from the insoluble fraction.  They published their results in 1998.  The identification of claudin-1 and claudin-2 opened the doors for other claudins to be discovered.  Just before his death in 2005, the Tsukita lab also isolated tricellulin (Ikenouchi et al. J Cell Biol. 2005 Dec 19;171(6):939-45).  Tricellulin is the protein present in the tight junctions of a three-cell intersection.  While not an exhaustive list of Shoichiro Tsukita’s contributions to science, these are some of the most important.

In his book Claudins, Shoichiro Tsukita spoke of his colleagues with great respect.  He acknowledged how they influenced him throughout his life.  He also spoke of vision.  He thought vision, or an understanding of the importance of the work, was necessary to be able to make important discoveries.  Shoichiro Tsukita definitely demonstrated that vision.

Read My Little Tale of the Discovery of the Claudins by Shoichiro Tsukita