Recombinant Human Neuroligin 4/NLGN4 Protein, CF

Neuroligin 4 (NLGN4, NL4 or NL4X) is a 110 kDa type I transmembrane glycoprotein that is a member of the type-B carboxyesterase/lipase family of proteins (1). Neuroligins are postsynaptically expressed on neurons and initiate excitatory presynapse maturation through binding to select isoforms of beta-neurexin (1 - 3). The 816 amino acid (aa) human NLGN4 contains a 41 aa signal sequence, a 635 aa extracellular domain (ECD), a 21 aa transmembrane domain and a 119 aa cytoplasmic tail. The ECD possesses a nonfunctional esterase homology domain through which neuroligins, except for NLGN2, interact with neurexins (4). Human NLGN4 is found on the X-chromosome. It shares 69% - 73% aa identity with NLGNs 1, 2 and 3, and 98% aa identity with NLGN4Y, a Y-chromosome-encoded neuroligin (1). Human NLGN4 ECD shares 62%, 99% and 99% aa identity with mouse, equine and canine NLGN4, respectively (5). Unlike other neuroligins, human NLGN4 does not appear to express alternate splice forms (1, 6). Crystalization of the NLGN4 ECD with and without beta-neurexin shows that NLGN4 forms a homodimer via a hydrophobic interface, but interactions with beta-neurexin are hydrophilic and calcium-dependent (4, 6). NLGNs 3 and 4 bind syntrophin-gamma 2 intracellularly (7). Mutations of NLGN4 can be associated with rare cases of autism, Asperger or Tourette syndromes (8 - 10). Mice with a loss-of-function mutation in NLGN4 show deficits in reciprocal social interactions and communication that are reminiscent of autism spectrum conditions in humans (11).