Recombinant Human LRRTM4 Protein, CF

LRRTM4 (Leucine-rich repeat transmembrane protein 4) is a member of the LRRTM family of molecules (1). All LRRTMs are type I transmembrane proteins that contain multiple leucine rich repeats, one PDZ consensus cytoplasmic binding domain, and show expression somewhere in the central nervous system. The LRRTM family is iterated across vertebrate (but not invertebrate) species. Human LRRTM4 is synthesized as a 590 amino acid (aa) precursor that contains a 30 aa signal sequence plus a 560 aa mature region. The mature molecule contains a 394 aa extracellular domain (aa 31 ‑ 424), a 21 aa transmembrane segment, and a 105 aa cytoplasmic region (1, 2). The extracellular domain is characterized by the presence of ten Leu-rich repeats, flanked by two cysteine-rich flanking sequences. Based on other LRRTMs, eukaryotic expression of LRRTM4 will likely yield an 82 ‑ 86 kDa glycosylated molecule (3, 4). There are at least two splice variants. Both show a Val substitution for aa 518 ‑ 590, one of which is also coupled to an alternative start site at Met312 (5, 6). Mature human LRRTM4 is 95% aa identical to mouse LRRTM4 (1). LRRTM4 is widely expressed, occurring in embryonic distal limb bud mesenchyme plus anterior sclerotome, and in adult testis, lung, muscle and prostate (1, 7). All LRRTMs are also found in brain. LRRTM4 has been identified in adult granular and mitral neurons of the olfactory bulb, neurons of cerebral cortex layers 2, 4, 5 and 6, and on neurons of the dentate gyrus (1). Functionally, it appears that LRRTM4 is involved in both pre-and post-synaptic modeling. Although embedded in the postsynaptic membrane, LRRTM4 seems to induce excitatory/glutamatergic presynaptic differentiation. Postsynaptically, LRRTM4 likely facilitates excitatory synapse formation on dendrites, acting in conjunction with multiple ligand-receptor combinations. In particular, the NR1 NMDA subunit has been shown to coalesce, or aggregate, in regions that experience LRRTM4 clustering (3, 8).