Conserved domain structure of β-neurexins: Unusual cleaved signal sequences in receptor-like neuronal cell-surface proteins

Y. A. Ushkaryov, Y. Hata, K. Ichtchenko, C. Moomaw, S. Afendis, Clive A. Slaughter, T. C. Sudhof

Research output: Contribution to journalArticlepeer-review

135 Scopus citations


Neurexins, a family of neuronal cell-surface proteins, consist of the longer α-neurexins (Iα, IIα, and IIIα) and the shorter β-neurexins (Iβ and IIβ) with identical C termini but distinct N termini. α-Neurexins have the structure of cell surface receptors, but the membrane topology and conservation of β-neurexins is unknown. We have now characterized cDNA clones encoding bovine neurexins Iβ and IIIβ, thereby demonstrating the presence of a β-form for neurexin III and the evolutionary conservation of β-neurexins in mammals. Similar to α-neurexins, β-neurexins were found to be highly O-glycosylated after expression by transfection in COS cells, suggesting that α- and β-neurexins utilize the same O-glycosylation cassette and have similar transmembrane orientations. To determine if β-neurexins contain a cleaved or uncleaved signal sequence for membrane translocation, β-neurexin-IgG fusion proteins were expressed in COS cells, and their N termini were directly sequenced. This revealed that the N terminus of all three β-neurexins contains an unusual cleaved signal sequence. Together our data show that all known neurexin genes generate α and β forms with similar transmembrane organizations and receptor-like structures. Due to the presence of a long atypical cleaved signal peptide, β-neurexins contain only a short unique sequence before splicing into the α-neurexin sequence. Thus, β-neurexins are essentially N terminally truncated α-neurexins.

Original languageEnglish (US)
Pages (from-to)11987-11992
Number of pages6
JournalJournal of Biological Chemistry
Issue number16
StatePublished - Apr 22 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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