High impact information on Nrxn1

• Surprisingly, neurexin also induces GABA postsynaptic differentiation [1].
• We show here that neurexin alone is sufficient to induce glutamate postsynaptic differentiation in contacting dendrites [1].
• The structure of the ligand-binding domain of neurexin Ibeta: regulation of LNS domain function by alternative splicing [2].
• Each gene uses alternative promoters and multiple variably spliced exons to potentially generate more than a 100 different neurexin transcripts [3].
• Neurexin mediates the assembly of presynaptic terminals [4].

Biological context of Nrxn1

• Alpha-latrotoxin is thought to trigger exocytosis by binding to CL1, while the role of neurexin 1alpha is uncertain [5].
• We conclude that neurexin 1beta and neuroligin 1 (and, by extension, other beta-neurexins and neuroligins) function as heterophilic cell adhesion molecules in a Ca2+-dependent reaction that is regulated by alternative splicing of beta-neurexins [6].
• Binding properties of neuroligin 1 and neurexin 1beta reveal function as heterophilic cell adhesion molecules [6].
• The interaction of the synaptic vesicle protein, synaptotagmin, and the presynaptic alpha-latrotoxin receptor, a neurexin, has been proposed to be involved in docking of synaptic vesicles at active sites or modulation of neurotransmitter release [7].
• We show here that glycosylation processing of neuroligin, in addition to mRNA splicing and gene selection, contributes to the specificity of the neurexin-beta/neuroligin-1 association [8].

Anatomical context of Nrxn1

• Kv1 (mammalian Shaker family) potassium channels and the neurexin Caspr2, both of which contain COOH-terminal PDZ domain binding peptide motifs, are found colocalized at high density at juxtaparanodes flanking nodes of Ranvier of myelinated axons [9].
• Moreover, overexpression of the homologous neurexin I ligand, neuroligin-1, restored both neurite extension and expression of neurexin Ialpha [10].
• However, this mutant still binds to major LTX receptors (latrophilin and neurexin) and causes strong transmitter exocytosis in synaptosomes, hippocampal slice cultures, neuromuscular junctions, and chromaffin cells [11].

Associations of Nrxn1 with chemical compounds

• Using intracellular [Ca(2+)] measurements both calcium-independent receptors for latrotoxin (CIRL or latrophilin) and neurexin 1 alpha receptors were found to be functionally present [12].

Physical interactions of Nrxn1

• On the structure of the 'synaptosecretosome'. Evidence for a neurexin/synaptotagmin/syntaxin/Ca2+ channel complex [13].
• To test this hypothesis, we used conditions (substitution of Ca2+ in the medium with Sr2+) under which LTXN4C does not bind to any member of the neurexin family but still interacts with latrophilin [11].

Other interactions of Nrxn1

• Synaptic cell adhesion and synaptogenesis are thought to involve the interaction of neuroligin, a postsynaptic transmembrane protein, with its presynaptic ligand neurexin [14].
• Synaptic targeting of neuroligin is independent of neurexin and SAP90/PSD95 binding [14].

Analytical, diagnostic and therapeutic context of Nrxn1

• Affinity chromatography experiments demonstrated that Caskin 1 coassembles with CASK on the immobilized cytoplasmic tail of neurexin 1, suggesting that CASK and Caskin 1 coat the cytoplasmic tails of neurexins and other cell-surface proteins [15].
• Neurexin III alpha is highly homologous to neurexins I alpha and II alpha and shares with them a distinctive domain structure that resembles a cell surface receptor. cDNA cloning and PCR experiments revealed alternative splicing at four positions in the mRNA for neurexin III alpha [16].

References