Research Projects

1) Regulation of intracellular membrane traffic by small GTPases：
Normal functions of a human body, which consists of ~6.0 X 1013 cells, rely strictly on the normal function of every cell. There are a variety of intracellular organelles, where specific proteins are present. Furthermore, it is essential for each cell to function properly that each protein is transported from an organelle where it is synthesized to another organelle or the plasma membrane where it fulfills its function.
Transport of proteins between secretory organelles, including the endoplasmic reticulum, the Golgi apparatus, endosomes and lysosomes, and the plasma membrane are mediated by membrane-enclosed structures, primarily carrier vesicles (Fig. 1). These transport processes are known generically as “membrane traffic”. Carrier vesicles are formed at a donor organelle by accumulation of cargo proteins and assembly of coat proteins (Fig. 2, green) under the control of the Arf family of small GTPases (Fig. 2, red). These vesicles subsequently fuse with an appropriate acceptor organelle to deliver the cargo molecules under the control of another family of small GTPases, Rabs (Fig. 2, blue).
		Fig. 1. Vesicular transport
	Transport processes between the trans-Golgi network (TGN), endosomes and the plasma membrane are extremely complicated (Fig. 2). Because there are ~20 Arf members and ~60 Rab members in mammals, these transport processes undergo complex regulation of these small GTPases and coat proteins. By focusing upon the functions of Arfs, Rabs and coat proteins, our research group aims at elucidation of the regulation of membrane traffic, in particular at the TGN and endosome levels.
Fig. 2. Sorting of proteins at the TGN and endosomes

2) Regulation of mitosis and cytokinesis by membrane traffic：
During cell division, intracellular organelles undergo disassembly, reassembly and dynamic relocalization, and are distributed equally into two daughter cells (Fig. 3). Because these mitotic processes require supply and removal of specific proteins and biological membranes, morphological changes in the organellar structures during mitosis are under the regulation of membrane traffic.
Several of small GTPases in the Arf and Rab families and their effector proteins are localized on the Golgi apparatus, recycling endosomes, the central spindle and the midbody during mitosis and cytokinesis. Localization of these proteins changes temporally and spatially. Our research group aims at elucidation of the roles of membrane traffic in the spatial and temporal regulation of cellular functions including mitosis.
		Fig. 3. Localization of intracellular organelles during cell division