LIMR, the prototype of a novel family of endocytic receptors

All organisms have to deal with molecules which are hardly soluble in aqueous solutions. These include lipids, fatty acids, hormones and numerous other important signaling molecules, such as retinoids, pheromones or odorants. Therefore they have evolved a sophisticated transport system to handle these molecules. This system consists of several groups of specific transport proteins. One of them are lipocalins, a large family of small, mostly extracellular proteins which are able to bind and transport a large variety of hydrophobic molecules of all chemical classes. They are found in vertebrates and invertebrate animals, plants and bacteria. Lipocalins have been implicated in a number of important biological processes, including modulation of cell growth and metabolism, detoxification processes, inflammation, regulation of immune response, tissue development or animal behaviour. Whereas the structural basis of the interaction of lipocalins with their hydrophobic ligands is well understood now, there is a major lack of knowledge of the mechanisms by which lipocalins exert their biological effects, since there is only limited knowledge about lipocalin-specific cell receptors. We have recently identified and cloned the first authentic gene encoding a lipocalin receptor (LIMR) from human. Genome searching reveals that there is in fact a family of related genes, present in almost all higher organisms. We were able to demonstrate that this lipocalin- receptor acts as an endocytic receptor and is therefore the prototype of a novel family of receptors.. Therefore, this project is outlined to increase our knowledge of the molecular mechanism of a quite novel system widely used in a number of signaling and sensory processes in eukaryotes. Main topics of this project are to find out whether LIMR is a specific lipocalin receptor or a multifunctional receptor, able to bind a broad spectrum of protein ligands. We would also like to deduce the mechanism of ligand targeting within the cell and analyze proteins involved in this process. In addition, the ligand spectrum and function of the LIMR orthologous human Dif14 and mouse Limbr1 will be investigated. Since lipocalins are of significant interest in biotechnology as specific drug carriers or drug targeting and delivery system, our project on lipocalin receptors might also be of relevance for this particular field of research.

All organisms have to deal with molecules which are hardly soluble in aqueous solutions. These include lipids, fatty acids, hormones and numerous other important signaling molecules, such as retinoids, pheromones or odorants. Therefore they have evolved a sophisticated transport system to handle these molecules. This system consists of several groups of specific transport proteins. One of them are lipocalins, a large family of small, mostly extracellular proteins which are able to bind and transport a large variety of hydrophobic molecules of all chemical classes. They are found in vertebrates and invertebrate animals, plants and bacteria. Lipocalins have been implicated in a number of important biological processes, including modulation of cell growth and metabolism, detoxification processes, inflammation, regulation of immune response, tissue development or animal behaviour. Whereas the structural basis of the interaction of lipocalins with their hydrophobic ligands is well understood now, there is a major lack of knowledge of the mechanisms by which lipocalins exert their biological effects, since there is only limited knowledge about lipocalin-specific cell receptors. We have recently identified and cloned the first authentic gene encoding a lipocalin receptor (LIMR) from human. Genome searching reveals that there is in fact a family of related genes, present in almost all higher organisms. We were able to demonstrate that this lipocalin- receptor acts as an endocytic receptor and is therefore the prototype of a novel family of receptors.. Therefore, this project is outlined to increase our knowledge of the molecular mechanism of a quite novel system widely used in a number of signaling and sensory processes in eukaryotes. Main topics of this project are to find out whether LIMR is a specific lipocalin receptor or a multifunctional receptor, able to bind a broad spectrum of protein ligands. We would also like to deduce the mechanism of ligand targeting within the cell and analyze proteins involved in this process. In addition, the ligand spectrum and function of the LIMR orthologous human Dif14 and mouse Limbr1 will be investigated. Since lipocalins are of significant interest in biotechnology as specific drug carriers or drug targeting and delivery system, our project on lipocalin receptors might also be of relevance for this particular field of research.