title: The first gamma-carboxyglutamate-containing neuropeptide.
abstract: 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 gamma-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 gamma-carboxy D-peptide appears to be the first reported carboxylated neuropeptide.
authors.affiliation: Department of Chemistry and the Beckman Institute, University of Illinois, Urbana, 61801, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Jakubowski
authors.forename: Nathan G
authors.initials: NG
authors.lastname: Hatcher
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Sweedler
mesh_terms: D015055:1-Carboxyglutamic Acid / Q000032:analysis* / Q000737:chemistry* / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000032:analysis* / Q000737:chemistry* / Q000235:genetics
chemical_list: D009479:Neuropeptides; D015055:1-Carboxyglutamic Acid