Mouse models gnaw away at mystery of immune function
The molecular mechanisms underlying the interaction of mast cell granules with plasma membrane are not well understood. 'The role of membrane trafficking in immune cell function' (Membrane dynamics) is a project that has set out to discover and test the primary factors involved in the regulation and biology of membrane trafficking and signal compartmentalisation. Specifically, researchers are analysing the biological function of two regulators of small guanosine triphosphatases (GTPases), a large family of catalyst enzymes that separate the water molecules of guanosine triphosphate (GTP). These regulators are RIN3 and ACAP1 and are involved in membrane trafficking and the regulation of the actin cytoskeleton. The actin cytoskeleton is a dynamic network central to the movement and shape determination of cells. In addition to studying the biological function of these molecules, project partners are also focusing on what role they play in the development of allergy/asthma and autoimmunity. In studies performed to date, the focus has been on analysing the gene expression profile of RIN3 and ACAP1 in immune cells. Intricate gene expression studies using a mouse model revealed a high expression of RIN3 in mast cells and dendritic cells. However, while RIN3 was hardly detectable in other immune cells, ACAP1 gene expression was highest in T and B lymphocytes and also expressed in macrophages and dendritic cells. Ongoing studies of RIN3 under varying circumstances reveal an inhibitory function on mast cell degranulation and identify it as a negative regulator of mast cell function. The research team has cloned murine RIN3 for future use in overexpression studies that aim to further define the cellular function of RIN3. As work continues, Membrane dynamics is working to generate RIN3-deficient mice, which will open up new prospects of generating mouse disease models for research into allergy/asthma.