In 1970 Takeichi became a member of the faculty of Kyoto University, and he served as Professor of Biophysics from 1986 to 2002. During his time at Kyoto, he studied abroad at the Carnegie Institute Department of Embryology for a fellowship. In 2000, he was appointed as Director of the RIKEN Center for Developmental Biology.
Research contributions
In 1977 Takeichi discovered cadherin, and since then he has contributed to clarify its functions in tissue construction and to understand the molecular mechanisms of cell adhesion. After his discovery of cadherins, he continued to research cadherins and their properties. Along with cadherins, he also researched cell junctions and adhesions. He continues to research at RIKEN today.
Discovery of the Cadherin Family
While first working in Kyoto, Takeichi was using trypsin to study cell adhesions and aggregation. Once he moved to the Carnegie Institution, he realized the trypsin he was using behaved differently. This trypsin solution contained EDTA, along with the trypsin, which disturbed adhesion. The EDTA sequesters calcium ions, so Takeichi began testing for adhesion dependent on calcium. He used Chinese Hamster V79 cells and treated them with a variety of treatments, including EDTA, trypsin + EDTA, and trypsin + calcium. Once treated, these cells were tested for aggregation levels. He found that both calcium dependent and calcium independent pathways existed, and that the calcium treatment prevent trypsin's effects on the cell. Takeichi knew there was calcium dependent molecule that served an important role, but he had to find it. Rolf Kemler's anti serum was what helped him finally identify cadherin. E-cadherin was the first of the cadherin family to be discovered. During this research, Takeichi also observed changes in the morphology of the cells involved with adhesions. He accurately hypothesized that the adhesions dependent on calcium played a role in managing cells' morphogenetic behavior. His discovery of the cadherin family led to a developing field of studying adhesions pathways.
Other contributions
Takeichi, along with other scientists, studied the mechanism behind hemagglutinin from Botulism and its effect on the epithelial barrier of the intestines. They found the hemagglutinin directly interacted with the e-cadherin in the epithelial cells to disturbed cell to cell adhesion. This interaction like cell to cell adhesion is dependent on calcium ions. An assay showed the hemaglutinin interaction is specific to e-cadherin. Outside of cadherin, Takeichi studied other molecules involved with cell adhesion and beyond. He studied alpha-catenin functions outside of their functions within cell adhesion. The results showed alpha-catenin have a variety of functions outside of cadherin and adhesion. It regulates multiple different molecules, like actin and RhoGEF.
