High impact information on NRXN1

• Neuroligation: building synapses around the neurexin-neuroligin link [1].
• The three-dimensional structures of LG/LNS domains from neurexin, the laminin alpha 2 chain and sex hormone-binding globulin reveal a close structural relationship to the carbohydrate-binding pentraxins and other lectins [2].
• Thousands of neurexin isoforms are generated from three genes by usage of alternative promoters and alternative splicing [3].
• This review describes the properties of the neurexin protein family and their potential roles in neuronal cell adhesion and intercellular signaling [3].
• Our study nominates several novel genes, such as Neurexin 1 (NRXN1), in the development of nicotine dependence while also identifying a known candidate gene, the beta3 nicotinic cholinergic receptor [4].

Biological context of NRXN1

• Analysis of the human neurexin genes: alternative splicing and the generation of protein diversity [5].
• Although mammalian genomes contain only three neurexin genes, thousands of neurexin isoforms may be expressed through the use of two alternative promoters and alternative splicing at up to five different positions in the pre-mRNA [5].
• In total, we isolated 144 cosmids from this region and generated a sequence-ready cosmid contig of the approximately 500-kb region between the neurexin locus and D11S2196E [6].
• Synaptotagmin I and neurexin I mRNAs, coding for proteins involved in neurotransmitter secretion, become detectable in primary sympathetic ganglia shortly after initial induction of the noradrenergic transmitter phenotype [7].

Anatomical context of NRXN1

• In contrast, the mRNA encoding for neurexin-Ibeta, the heterophilic ligand of the AChE-homologous neuronal cell surface protein neuroligin, was drastically lower in embryonic transgenic spinal cord than in controls [8].
• Neuroligin is a neural cell-adhesion molecule of the post-synapse, which binds to the presynapse molecule neurexin to form a heterotypic intercellular junction [9].
• Higher temperatures facilitate insertion of the toxin into the plasma membrane, where it co-localizes with latrophilin (under all conditions) and with neurexin (in the presence of Ca(2+)) [10].
• However, the toxin induces pores efficiently in COS-7 cells transfected with the heptahelical receptor latrophilin or the monotopic receptor neurexin [10].
• Latrophilin, neurexin, and their signaling-deficient mutants facilitate alpha -latrotoxin insertion into membranes but are not involved in pore formation [10].

Associations of NRXN1 with chemical compounds

• Interestingly, on subsequent removal of Ca(2+), alpha-latrotoxin dissociates from neurexin but remains in the membrane and continues to form pores [10].
• In skeletal muscle, dystroglycan is a component of the dystrophin-glycoprotein complex. alpha-Dystroglycan is an extracellular peripheral membrane glycoprotein that binds to beta-dystroglycan, which is a transmembrane glycoprotein. alpha-Dystroglycan is heavily glycosylated and its sugars have a role in binding to laminin, neurexin and agrin [11].

Physical interactions of NRXN1

• The three-dimensional models of the AF-6 PDZ-Neurexin C-terminal peptide complex and the AF-6 PDZ-Bcr C-terminal peptide complex were built up by molecular dynamics simulations [12].
• The paired, but not the isolated PDZ domains of syntenin bind also strongly to the immobilized cytoplasmic domains of neurexin and B-class ephrins [13].

Other interactions of NRXN1

• Unexpectedly, two of these, NRXN1 ( approximately 1.1 Mb) and NRXN3 ( approximately 1.7 Mb), are among the largest known human genes [5].
• Solution structure of AF-6 PDZ domain and its interaction with the C-terminal peptides from Neurexin and Bcr [12].
• Neuroligin and neurexin form an intercellular adhesion complex sufficient to trigger formation of functional presynaptic elements in vitro [14].
• We report the expression of neurexin 1, Neuro D1, dlx1, and dlx2 in untreated and cAMP treated epithelial prostate cells [15].
• Recently, the three-dimensional (3D) structure of LG domains from plasma SHBG, laminin and neurexin have been reported and were found related to the pentraxin family [16].

Analytical, diagnostic and therapeutic context of NRXN1

• In situ hybridizations revealed unaltered expression of neurofilament (NF-160), synaptotagmin I and neurexin I in adrenal glands [17].

References