The making of neurexins.
Neurexins are neuronal cell-surface proteins with up to thousands of isoforms. These isoforms are generated by alternative splicing of transcripts from six promoters in three genes. The structure of neurexins resembles cell-surface receptors with a modular architecture suggestive of a sequential assembly during evolution. Neurexins probably perform multiple functions in the brain. They participate in intercellular junctions in which beta-neurexins tightly bind to a second class of neuronal cell-surface receptors called neuroligins. Intracellularly, the neurexin/neuroligin junction is bound by CASK on the neurexin side and PSD95 on the neuroligin side. CASK and PSD95 are homologous membrane-associated guanylate kinases that bind to the neurexin/neuroligin junction via PDZ domains, creating an asymmetric junction (neurexin/neuroligin) with similar intracellular binding partners. In addition to a function as cell-adhesion molecules, neurexins may also serve as a signalling receptor, because a class of ligands for alpha-neurexins called neurexophilins is similar to peptide hormones. Finally, at least one neurexin isoform, neurexin Ialpha, represents a high-affinity receptor for alpha-latrotoxin, which is a potent excitatory neurotoxin. Thus, neurexins constitute a large family of neuronal receptors that may be involved in multiple interactive functions between neurons.
Missler
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Department of Molecular Genetics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Fernandez-Chacon
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R
Südhof
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TC
D000595:Amino Acid Sequence; D000818:Animals; D006023:Glycoproteins; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009479:Neuropeptides; D017386:Sequence Homology, Amino Acid
D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C093175:neurexin II; C082354:neurexin IIIalpha; C112162:neurexophilin