Recombinant Human LRRN3/NLRR-3 Protein, CF

Neuronal leucine-rich repeat 3 (NLRR-3) is an 85 kDa, N-glycosylated member of a CNS-associated family of transmembrane molecules that includes AMIGO, FLRT, LINGO, LRIG, SLITRK, and Trk subgroups (1, 2). Mature human NLRR-3 consists of a 606 amino acid (aa) extracellular domain (ECD) with 13 LRRs, an RGD integrin-binding motif, one Ig-like domain, and one fibronectin type III-like domain, a 21 aa transmembrane segment, and a 59 aa cytoplasmic domain (3). Within the ECD, human NLRR-3 shares 91% aa sequence identity with mouse and rat NLRR-3. NLRR-3 is expressed in specific areas of the developing and adult CNS, and more weakly in other tissues including lung, liver, kidney, and adrenal gland (2 - 5). It is preferentially expressed in the third layer of the cerebral cortex in contrast to other NLRRs which are more diffusely distributed between cortical layers (6). During mouse development, its expression pattern is generally complementary to that of SLITRK6 in select brain regions, plus the cochlea, eye, tongue, teeth, and nasal mesenchyme (7). NLRR-3 is upregulated in the cerebral cortex following injury (3, 6). Its expression is dependent on NGF stimulation and is strongest in NGF responsive TrkA⁺ neuroblastoma cell lines that are weakly aggressive (3). The cytoplasmic domain of NLRR-3 contains two Yxxf motifs which are required for its clathrin-mediated internalization (8). The association of NLRR-3 with clathrin and beta-adaptin promotes the enhancement and prolongation of EGF induced signaling (8).