Recently, receptor signal transduction has been identified to occur not only at the plasma membrane, but also at various intracellular compartments. Hence, receptor trafficking and signal compartmentalization may contribute to a higher level of cellular organization. The proposal’s objective is to understand fundamental principals in the regulation and biology of membrane trafficking and signal compartmentalization, and to test them in a physiological context. The overall research concept is to study two immune specific regulators for small GTPases, RIN3 and ACAP1, which are involved in the regulation of membrane trafficking and the actin cytoskeleton. In a functional genomic approach, mice deficient for these genes will be generated and lymphocyte signaling and immune cell function/development will be used as a physiological read out to study the biological role of signal compartmentalization. The analysis of knock-out mice will be complemented by biochemical in vitro experiments to further dissect molecular mechanisms of RIN3/ACAP1 function. In addition the potential role of these molecules in the development of immune disorders, such as allergy/asthma will be analyzed. Thus, the study will provide novel insights into the complexity of functions regulated by signal compartmentalization, may have far reaching implications for our understanding of immune cell function in health and disease, and may offer an opportunity to develop novel therapeutical strategies in autoimmunity. The researcher is an internationally experienced and well recognized expert for membrane dynamics and trafficking. The proposed theme regarding the physiologic relevance of membrane dynamics demonstrates a high degree of originality and innovation in a very promising research field. The host, the Research Center Borstel, is characterized by an interdisciplinary approach combining basic sciences with clinical research providing an ideal scientific environment to conduct the proposed work.
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