The first gamma-carboxyglutamate-containing neuropeptide

Neurochemistry International
Jennifer A JakubowskiJ V Sweedler

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.

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Citations

Aug 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nathan G HatcherJonathan V Sweedler
Aug 25, 2015·General and Comparative Endocrinology·Samuel D RobinsonHelena Safavi-Hemami
Jul 19, 2008·Annual Review of Analytical Chemistry·Lingjun Li, Jonathan V Sweedler
Aug 28, 2009·Radiation Research·Juliann G KiangNeil G Agravante
Nov 16, 2007·Journal of Neurophysiology·Nathan G Hatcher, Jonathan V Sweedler
Mar 3, 2007·The Biochemical Journal·Carolina Möller, Frank Marí
Feb 5, 2021·ACS Chemical Biology·Md Shadman Ridwan AbidJames W Checco
Aug 19, 2008·Analytical Chemistry·Stanislav S Rubakhin, Jonathan V Sweedler
Mar 18, 2008·Analytical Chemistry·Michael A EwingJonathan V Sweedler

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