LIMR, a prototype of a novel class of endocytic receptors

Based on their ability to bind small hydrophobic molecules lipocalins were found to be involved in a number of important physiological processes. However, whereas the biochemical features of lipocalins are well characterized by now, there is a lack of understanding of the precise mechanism by which lipocalins exert their biological effects. This lack of knowlegde is mostly due to the fact that some major mechanisms, e.g. delivering of the ligand and receptor binding are poorly characterized so far. We have identified and characterized a novel human membrane receptor (LIMR) which specifically interacts with human lipocalin-1. Very recently we found that this receptor mediates the internalization of this lipocalin member. Sequence analysis and topographical modeling revealed the presence of a number of putative LIMR homologous and orthologous proteins in several organisms, suggesting that LIMR is a prototype of a novel class of endocytic receptors. These results set the stage for exploring the molecular mechanism of the lipocalin-receptor interaction in detail and allow us to address a number of important questions concerning lipocalin-receptor interaction in general. Therefore the aim of this project is to define, whether LIMR is a receptor specific for lipocalin-1, specific for several lipocalins or rather a multifunctional receptor, able to bind a broad spectrum of ligands. To deduce the ligand pathway within the cell, intracellular LIMR interacting proteins will be isolated. Concerning lipocalin- receptor interaction in general ultrastructural analysis should be perfomed to characterize the endocytotic pathway of LIMR. In addition, investigation on the ligand spectrum of the LIMR orthologous human Dif14 should provide a deeper insight into the physiological function(s) of this novel family of membrane receptors.