The first γ-carboxyglutamate-containing neuropeptide

Jennifer A. Jakubowski, Nathan G. Hatcher, Fang Xie, Jonathan V. Sweedler

Research output: Contribution to journalArticlepeer-review


A key factor in the characterization of peptide transmitters used in neuronal signaling is the correct elucidation of post-translational modifications, especially as they are often required to confer biological activity. A rare carboxylation modification is described on the D-peptide from the insulin prohormone in the sea slug, Aplysia californica. Using liquid chromatography purification coupled with electrospray ionization and nanoelectrospray ionization-ion trap-mass spectrometry (ESI- and nanoESI-MS), the presence of this D-peptide within Aplysia insulin (AI)-producing neurons is confirmed. Further detailed mass spectrometric analyses demonstrate that the Aplysia insulin D-peptide is carboxylated on the single glutamate residue within the sequence. This γ-carboxy D-peptide, along with other identified AI-related peptides, is secreted from the central nervous system in response to ionophore stimulation, thus suggesting a signaling role within the nervous system. Although carboxylated peptides have been described previously, the Aplysia γ-carboxy D-peptide appears to be the first reported carboxylated neuropeptide.

Original languageEnglish (US)
Pages (from-to)223-229
Number of pages7
JournalNeurochemistry International
Issue number3
StatePublished - Aug 2006


  • Aplysia californica
  • Insulin
  • Invertebrate
  • Mass spectrometry
  • Post-translational modification

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience


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