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 journalArticle

115 Citations (Scopus)

Abstract

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
Volume269
Issue number16
StatePublished - Jan 1 1994
Externally publishedYes

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Protein Sorting Signals
Membrane Proteins
COS Cells
Conservation
Glycosylation
Membranes
Mammals
Cell Surface Receptors
Transfection
Fusion reactions
Complementary DNA
Clone Cells
Immunoglobulin G
Genes
Topology
signal sequence receptor
Proteins
neurexin II

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ushkaryov, Y. A., Hata, Y., Ichtchenko, K., Moomaw, C., Afendis, S., Slaughter, C. A., & Sudhof, T. C. (1994). Conserved domain structure of β-neurexins. Unusual cleaved signal sequences in receptor-like neuronal cell-surface proteins. Journal of Biological Chemistry, 269(16), 11987-11992.

Conserved domain structure of β-neurexins. Unusual cleaved signal sequences in receptor-like neuronal cell-surface proteins. / Ushkaryov, Y. A.; Hata, Y.; Ichtchenko, K.; Moomaw, C.; Afendis, S.; Slaughter, Clive A.; Sudhof, T. C.

In: Journal of Biological Chemistry, Vol. 269, No. 16, 01.01.1994, p. 11987-11992.

Research output: Contribution to journalArticle

Ushkaryov, YA, Hata, Y, Ichtchenko, K, Moomaw, C, Afendis, S, Slaughter, CA & Sudhof, TC 1994, 'Conserved domain structure of β-neurexins. Unusual cleaved signal sequences in receptor-like neuronal cell-surface proteins', Journal of Biological Chemistry, vol. 269, no. 16, pp. 11987-11992.
Ushkaryov, Y. A. ; Hata, Y. ; Ichtchenko, K. ; Moomaw, C. ; Afendis, S. ; Slaughter, Clive A. ; Sudhof, T. C. / Conserved domain structure of β-neurexins. Unusual cleaved signal sequences in receptor-like neuronal cell-surface proteins. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 16. pp. 11987-11992.
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