Human ROBO1 ELISA Kit

Slit2 and Roundabout 1 (Robo1) provide a key ligand-receptor interaction for the navigation of commissural neurons during the development of the central nervous system. Slit2 is a large multidomain protein containing an unusual domain organization of four tandem leucine-rich repeat (LRR) domains at its N-terminus. These domains are well known to mediate protein-protein interactions; indeed, the Robo1-binding region has been mapped to the concave face of the second LRR domain. It has also been shown that the fourth LRR domain may mediate Slit dimerization and that both the first and second domains can bind heparin. Thus, while roles have been ascribed for three of the LRR domains, there is still no known role for the third domain. Each of the four LRR domains from human Slit2 have now been successfully expressed in milligram quantities using expression in mammalian cells. Here, the crystallization of the second and third LRR domains and the structure of the third LRR domain are presented. This is the first structure of an LRR domain from human Slit2, which has an extra repeat compared with the Drosophila homologue. It is proposed that a highly conserved patch of surface residues on the concave face may mediate any protein-protein interactions involving this LRR domain, a result that will be useful in guiding further studies on Slit2.

Odorants are detected by olfactory receptor neurons (ORNs) located in the olfactory epithelium. In mice, ORNs expressing the same odorant receptor ( OR) project to a single glomerulus out of 1800 in the olfactory bulb ( OB). It has been proposed that OR-derived cAMP signals guide ORN axons to their glomeruli rather than OR themselves. Recently, it has also been shown that the axon guidance molecule Slit1 and its receptor Robo2 control the dorsoventral segregation of ORN axons as they are projecting to the OB. We have analyzed the development of olfactory projections in Slit1/Slit2 and Robo1/Robo2 single and double mutants. We show that in Robo1(-/-); Robo2(-/-) mice, most ORN axons fail to enter the OB and instead project caudally into the diencephalon. Moreover, in these mice, ORN axons expressing the same OR project to several glomeruli at ectopic positions. Thus, Slit1, Slit2, Robo1, and Robo2 cooperate to control the convergence of ORN axons to the OB and the precise targeting of ORN axons to specific glomeruli.