Two novel mammalian Nogo receptor homologs differentially expressed in the central and peripheral nervous systems

The regenerative capacity of the adult mammalian central nervous system is restricted by the myelinating oligodendrocytes that form a nonpermissive environment for axonal growth. Currently only the Nogo receptor (NgR), in complex with p75(NTR) neurotrophin receptor is known to be involved in this inhibitory signalling in neurons. NgR is a common receptor for the three inhibitory myelin proteins Nogo-A, OMgp, and MAG. Here we describe two novel Nogo receptor gene homologs named NGRL2 and NGRL3 from human and mouse that, like NGR, encode putative leucine-rich repeat containing GPI-anchored proteins. We show by in situ hybridisation and by RT-PCR that NGRL mRNAs are predominantly expressed in the neurons of the embryonic and adult central and peripheral nervous systems, and that they together with NGR possess distinct and partially nonoverlapping expression patterns. We also show that all four members of the reticulon family, including Nogo-A, are widely expressed in the nervous system, and therefore are possible ligands for the NgRLs.