|Budget Amount *help
¥16,030,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2007: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2006: ¥10,700,000 (Direct Cost: ¥10,700,000)
The Rab family small G proteins, which consist of more than 60 different members in mammalian cells, are key regulators in membrane trafficking. Since each member recognizes distinct subsets on intracellular membranes, this family may contribute to temporal and spatial regulation of signal transduction in various cellular functions. In this project, we analyzed the functions of Rab proteins in neurotransmission, cell-cell adhesion, and cell growth. As to neurotransmission, we focused on the process of neurotransmitter release, which Rab3A and its related proteins regulate. We generated Rab3 GAP p130-deficient mice and showed using the mice that this protein plays important roles in neurotransmitter release and synaptic plasticity through regulation of the activity and translocation of Rab3A at the nerve endings. As to the cell-cell adhesion, we focused on the transport of the adhesion proteins to the cell-cell adhesion sites of the epithelial cells. We had previously found that Rabl3 regulates the transport of the integral adhesion proteins, claudins and occludin, to the tight junctions. In this project, we identified JRAB/MICAL-L2 as a novel Rabl3 effector protein, which localized to the tight junctions and found that the Rab13-JRAB system functions to establish the formation of the tight junctions. We moreover found that another Rab family member Rab8 also interacts with JRAB and that this interaction contributes to the assembly of adherens junctions through regulation of the transport of E-cadherin, an integral adherens junction protein. As to the cell growth, we showed that Rabring7, which we had identified as a novel Rab7 effector protein, has E3 ligase activity and that this protein is involved in the endocytic trafficking of EGF receptor through its E3 ligase activity.